Transfusion of leukoreduced blood products and risk of antibody-mediated rejection of renal allografts.

BACKGROUND: Antibody-mediated rejection (AMR) is a major barrier to the long-term function of renal allografts. White blood cells, which may be present in red blood cell (RBC) units, and platelets (PLTs) express HLA antigens that may increase the risk of AMR by inducing or increasing humoral sensitization to HLA. STUDY DESIGN AND METHODS: A retrospective cohort study of HLA-incompatible (HLAi) renal transplant recipients between 2004 and 2015 was conducted. Data on apheresis PLT and leukoreduced RBC transfusions within 4 weeks of transplantation, demographic information, and biopsy-proven AMR were collected from medical records and the Scientific Registry of Transplant Recipients. Patients were evaluated until they showed evidence of AMR or until 1 year posttransplant, whichever came first. Multivariable analysis with Cox modeling was performed. RESULTS: Of 244 individuals, 182 (74.6%) received RBCs and 20 (8.2%) of those also received PLTs. During the first year posttransplant, 97 (39.8%) had AMR. RBC-alone or RBC and PLT transfusions were not associated with increased risk of AMR after adjustment for panel-reactive antibody, years on dialysis, HLA antibody strength, and number of therapeutic plasma exchange treatments (adjusted hazard ratio [adjHR] 1.00, 95% confidence interval [95% CI] 0.59-1.69; and adjHR 0.68, 95% CI 0.28-1.68, respectively). For each 1-unit increase in RBC transfusions, there was no association with AMR (adjHR 0.94, 95% CI 0.85-1.05). Only HLA antibody strength before transplantation was associated with AMR (adjHR 2.23, 95% CI 1.10-4.52; cytotoxic crossmatch compared to crossmatch negative but detectable donor-specific HLA antibodies). CONCLUSIONS: Patients who receive an HLAi transplant who are transfused with leukoreduced RBCs or PLTs in the peritransplant period are at no higher risk of AMR than nontransfused patients.

Impact of flow cytometry in liver cytopathology.

BACKGROUND: Fine needle aspiration (FNA) is commonly used as a diagnostic tool for the evaluation of lymphoproliferative diseases. Cytomorphology alone is often insufficient for the diagnosis and subclassification of lymphoma; therefore, flow cytometry (FC) plays an important role in the characterization of lymphoproliferative disorders. This study reviews our experience with FC on liver FNA at the Johns Hopkins Hospital. METHODS: 2,424 liver FNAs performed over a 21-year period were reviewed for clinical FC data (n=74) or a subsequent diagnosis of lymphoma in the liver without FC data (n=40). RESULTS: In our study, 114 cases (4.7%) were included out of the 2,424 liver FNAs performed during the study period. Lymphoma was diagnosed 79 times. Cytomorphology alone was diagnostic of lymphoma in 45 cases, and in 33 cases both the cytomorphology and the FC were consistent with a diagnosis of lymphoma. Neither FC nor cytomorphology were diagnostic of lymphoma on 1 specimen. In 39 cases, FC had negative results on a lesion suspicious for lymphoma based on cytomorphology. In several nonlymphoma cases, FC provided information that allowed further subclassification of the neoplasm. CONCLUSION: FC is a useful adjuvant diagnostic test for liver FNAs performed on patients with lymphoproliferative disorders.

Recurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas: Molecular Characterization and Proposal for a Separate Classification.

Thyroid gland teratomas are rare tumors that span a wide clinicopathologic spectrum. Although benign and immature teratomas arise in infants and young children and generally have good outcomes, malignant teratomas affect adults and follow an aggressive course. This divergent behavior raises the possibility that benign/immature and malignant teratomas are separate entities rather than different grades of a single tumor. However, the histogenesis and molecular underpinnings of thyroid gland teratomas are poorly understood regardless of grade. In this study, we performed next-generation sequencing on 8 thyroid gland teratomas, including 4 malignant, 3 benign, and 1 immature. We identified DICER1 hotspot mutations in all 4 malignant cases (100%) but not in any benign/immature cases (0%). No clinically significant mutations in other genes were found in either group. We also performed immunohistochemistry to characterize the primitive components of malignant teratomas. Not only did all cases consistently contain immature neural elements (synaptophysin and INSM1 positive), but also spindled cells with rhabdomyoblastic differentiation (desmin and myogenin positive) and bland epithelial proliferations of thyroid follicular origin (TTF-1 and PAX8 positive). Although DICER1 mutations have previously been implicated in multinodular hyperplasia and well-differentiated thyroid carcinomas, these findings demonstrate the first recurrent role for DICER1 in primitive thyroid tumors. The combined neural, rhabdomyoblastic, and homologous epithelial elements highlighted in this series of malignant thyroid gland teratomas parallel the components of DICER1-mutated tumors in other organs. Overall, these molecular findings further expand the differences between benign/immature teratomas and malignant teratomas, supporting the classification of these tumors as separate entities.

Importance of Flow Cytometry in the Cytopathologic Evaluation of Lymphoid Lesions Involving the Kidney.

BACKGROUND: Cytomorphology alone is often insufficient for the diagnosis and subclassification of lymphomas, so flow cytometry (FC) may be used as an adjuvant test. METHODS: Renal fine-needle aspirations (FNAs) performed from January 1993 to August 2014 were reviewed for FC data or a diagnosis of lymphoma. RESULTS: A total of 586 renal FNAs were collected. Thirty-three cases (5.1%) had FC analysis. Lymphoma was diagnosed 35 times (6%), and FC was performed in 21 (60%) cases. Both cytomorphology and FC were consistent with lymphoma in 20 cases. Cytomorphology alone was diagnostic of lymphoma in 15 cases. In 28 cases, biopsy from the kidney or another site was diagnostic of lymphoma. One subsequent biopsy revealed that a kidney FNA, which showed no definitive morphologic or FC evidence of lymphoma, likely represented necrotic diffuse large B-cell lymphoma. CONCLUSION: FC is a useful adjuvant diagnostic test for renal FNAs, particularly for subclassification and confirmation of the diagnosis when there is insufficient material for immunohistochemistry. FC should be interpreted with caution when a sample is limited or when there is suspicion of Hodgkin lymphoma, and further work-up is warranted when cytomorphology suggests lymphoma but FC is negative.

Cerebrospinal fluid cytology of an endolymphatic sac tumor.

Endolymphatic sac tumor (ELST) is a rare neoplasm which is seldom evaluated by cytopathology. We report the clinicopathologic course and cytologic cerebrospinal fluid (CSF) findings in a 58-year-old patient with brainstem lesions who originally presented with vertigo but progressed to having left 7th, 8th, 9th, and 10th cranial nerve palsies, right-sided weakness, and occipital headaches. Cytospin of the CSF revealed large epithelioid cells similar to cells seen in a surgical resection of a brain mass three months previously. Review of the surgical specimen revealed a well-differentiated glandular and papillary neoplasm, most consistent with an endolymphatic sac tumor.