Statin-Induced Rhabdomyolysis Associated With Transjugular Intrahepatic Portosystemic Shunt Placement.

Rhabdomyolysis is a known rare and potentially lethal complication of statin use. This toxic effect is potentiated by alterations in hepatic physiology in patients with cirrhosis. Transjugular intrahepatic portosystemic shunt placement has the potential to further compound this effect; yet, examples of this have not previously been described in the literature. We present a case of a patient who experienced statin-induced rhabdomyolysis likely as a direct consequence of transjugular intrahepatic portosystemic shunt placement.

Infantile leukemia-What factors determine its distinct biological nature? Clinicopathological study of 78 cases.

INTRODUCTION: Infantile leukemia encompasses a heterogeneous group which needs stratifying for treatment selection. METHODS: We collected 78 cases of infantile leukemia and retrospectively analyzed their clinicopathological data. RESULTS: Infantile leukemia featured a ratio of acute myeloid leukemia (AML) to B-lymphoblastic leukemia (B-ALL) of 1:2, with a better survival for AML than B-ALL (median survival 36 vs 24 months). When stratified by age, "early" infantile B-ALL (2-6 months) showed a high rate of KMT2A rearrangement (100%), similar to the rate seen in congenital B-ALL (1 month) (100%) and higher than seen in "late" infantile B-ALL (≥7 months) (68%). The three categories of infantile B-ALL exhibited an age-dependent increase in survival (median survival 8.5, 24, and >24 months, respectively). The age-dependent survival benefit remained after excluding the cases negative for KMT2A rearrangement. Conversely, infantile AML lacked an age-dependent pattern of survival. CONCLUSION: The clinical outcome of infantile leukemia depends on the type of leukemia. Given the age-dependent survival, infantile B-ALL can be divided into three subcategories.

Analysis of clinicopathological and cytogenetic differences between B-lymphoblastic lymphoma and B-lymphoblastic leukemia in childhood.

Although considered the same disease by 2016 WHO Classification, B-ALL and B-LBL show different clinicobiologic behavior, with B-ALL manifesting as disseminated disease and B-LBL as a localized mass. Distinction between the two is based on an arbitrary cutoff of 25% bone marrow involvement. We reviewed clinical, immunophenotypic, and cytogenetic data in B-lymphoblastic neoplasms of childhood to explain the differences. Performing a retrospective review of 126 cases of B-ALL and 18 cases of B-LBL in patients ≤18 years, revealed the following significant differences: younger age of presentation for leukemia; increased cytogenetic abnormalities in leukemia than lymphoma, specifically increased recurrent genetic abnormalities, with the exception of ploidy aberrancy; and the observation that unfavorable recurrent genetic abnormalities occurred in B-ALL and only favorable abnormalities in B-LBL. Down syndrome presented with leukemia only. Findings demonstrated that pediatric B-ALL and B-LBL exhibit dissimilar genomic profiles, suggesting possible differences in pathogenesis between the two closely-related neoplasms.

Clinicopathologic and genetic spectrum of infantile B-lymphoblastic leukemia: a multi-institutional study.

Acute lymphoblastic leukemia (ALL) in infants <1-year-old is biologically different from ALL in older children. Although KMT2A rearrangement is the predominant genetic signature in infantile B-ALL, disease course is heterogenous, behaving more aggressively in younger infants. We investigated clinicopathological differences throughout the first year to understand the transition to pediatric B-ALL. In a multi-institutional review involving four medical institutions, 54 cases of infantile B-ALL were identified. Patients were divided into congenital and non-congenital groups with multiple age subgroups. Male predominance was seen in congenital cases compared to female in non-congenital cases. There were decreasing trends of hyperleukocytosis, central nervous system involvement, KMT2A rearrangements, lineage switch, and mortality, versus increasing trends of CD10 expression and non-KMT2A abnormalities. Statistically significant differences emerged at 3 and 9 months, the latter was not previously described. Poor-prognostic risk factors decreased with age, the last trimester of infantile B-ALL essentially merging with pediatric B-ALL.

Heterogeneity of Abnormal RUNX1 Leading to Clinicopathologic Variations in Childhood B-Lymphoblastic Leukemia.

OBJECTIVES: Abnormalities of the RUNX1 gene in childhood B-acute lymphoblastic leukemia (B-ALL) are manifested by ETV6-RUNX1 or RUNX1 amplification. A detailed comparison between the two regarding clinicopathologic features with genetic analysis has not been performed previously. This parallel study assessed how different RUNX1 abnormalities affect the clinicopathology of B-ALL. METHODS: We compared clinicopathologic factors, including age, sex, WBC count, cerebrospinal fluid (CSF) involvement, immunophenotype, and blast proliferation rate between B-ALL with RUNX1 amplification (10 cases) and B-ALL with ETV6-RUNX1 translocation (67 cases) in childhood B-ALL. RESULTS: CD7 was often expressed in RUNX1 amplification but not in ETV6-RUNX1 (44% vs 0%, P = .0001) and appeared to correlate with CSF involvement in the former group (3/4 [75%]). CD13 was often detected in ETV6-RUNX1 with additional RUNX1 gain (38%) with an even higher frequency in double ETV6-RUNX1 translocation (77%), but was not detected in RUNX1 amplification (0%, P < .05). Children with RUNX1 amplification were older and more often CSF positive, while those with ETV6-RUNX1 were younger, more frequently had hyperleukocytosis, and had higher blast proliferation rates. CONCLUSIONS: RUNX1 copy numbers seem to be proportional to the age of B-ALL onset and the frequency of CSF involvement, while RUNX1 amplification vs translocation causes aberrant expression of CD7 and CD13, respectively.

Clear cell urothelial carcinoma of the urinary bladder: a case report and review of the literature.

INTRODUCTION: The occurrence of clear cell tumors in the bladder is not uncommon. Clear cell dysplasia is well-described and characterized by focal replacement of transitional mucosa by cells with abundant clear cytoplasm, nuclear enlargement, and a granular chromatin pattern. Clear cells can also be seen in clear cell adenocarcinoma, which is rare, comprising 0.5% to 2.0% of the reported bladder carcinomas. Other clear cell tumors found in the bladder to be considered in the differential diagnosis are tumors of Müllerian origin and metastatic lesions, such as renal cell carcinoma, clear cell sarcoma, and malignant melanoma. Clear cell urothelial carcinoma is exceedingly rare, with only nine clinical cases described in the literature. CASE PRESENTATION: We report the case of a 75-year-old Caucasian man who presented with intermittent hematuria, in whom a bladder tumor was identified. A final histopathology examination of a cystoprostatectomy specimen revealed a pT3b, G3 urothelial carcinoma of clear cell type (>90% clear cells) and a prostatic adenocarcinoma of Gleason grade 3+3 (score=6). The bladder tumor consisted of sheets of malignant cells with severe nuclear atypia and abundant clear cytoplasm; no glandular or tubular structures were identified. Tumor cells were periodic acid-Schiff positive and negative after diastase treatment; additional mucicarmine and oil red O stains were negative. Immunohistochemical stains showed the tumor cells positive for cytokeratin 7 (CK7), p63 (>80% nuclei), p53 (about 30% nuclei), vimentin, E-cadherin, cluster of differentiation (CD10), and Ki-67 (>70% nuclei). Stains for cell adhesion molecule 5.2 (CAM 5.2), CD117, cytokeratin 20 (CK20), human melanoma black 45 (HMB-45), paired box protein (PAX 8), placental alkaline phosphatase (PLAP), prostate specific antigen (PSA), renal cell carcinoma (RCC), cancer antigen 25 (CA25), leukocyte common antigen (LC), S-100 protein, and uroplakin III were all negative. CONCLUSIONS: The tumor marker profile was consistent with clear cell type carcinoma of urothelial origin. Within the differential diagnoses, we ruled out other possible tumor types such as urothelial carcinoma with focal clear cell differentiation, clear cell adenocarcinoma, Müllerian tumors, and metastatic disease.

Severe lactic acidosis in a 14-year-old female with metastatic undifferentiated carcinoma of unknown primary.

A 14-year-old girl was found to have a large, non-tender breast mass with anemia and thrombocytopenia. The diagnosis of an undifferentiated carcinoma of unknown primary was made after open breast biopsy of the mass with negative immunohistochemical studies for breast malignancies. Further evaluation showed extensive metastatic disease affecting the bone marrow, ribs, liver, and brain with magnetic resonance imaging evidence of carcinomatous meningitis. Despite 2 months of chemotherapy and intensive supportive care, the patient died of severe lactic acidosis and disseminated intravascular coagulation after exaggerated menstrual bleeding. The association of severe lactic acidosis and undifferentiated carcinoma of unknown primary in an adolescent has not been previously described.