Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers.

OBJECTIVES: Stage I, grade 1 endometrial cancers have low recurrence rates and often do not receive adjuvant therapy. We compared recurrent cases to matched non-recurrent controls to evaluate for molecular markers associated with higher risk of recurrence. METHODS: A case-control study including all cases of recurrent stage I, grade 1 endometrioid endometrial cancer at one institution in a ten-year period. Cases were matched to controls by age, BMI, weight and stage. Molecular testing and immunohistochemistry were performed on archival tumor specimens: microsatellite instability (MSI-H), mismatch repair status, POLE mutational status, and next-generation sequencing. RESULTS: 15 stage I, grade 1 endometrial cancer cases with recurrent disease and available tumor specimens were identified. CTNNB1 and MSI-H were present at significantly higher rates in cases than controls (CTNNB1 60% vs. 28%, OR 3.9, 95%CI 1.1-14.7, p = 0.04 and MSI-H 53% vs. 21%, OR 4.4, 95%CI 1.1-17.0, p = 0.03). POLE mutations were found in 0% of cases vs. 7% of controls (p = 0.54). Among specimens demonstrating microsatellite stability (MSS), 100% of cases vs. 26% of controls had CTNNB1 mutations (p < 0.001). CTNNB1 wild type tumors were MSI-H in 100% of cases vs. 19% of controls (p < 0.001). CONCLUSIONS: Compared to controls, CTNNB1 mutation is present at significantly higher rates in recurrent stage I, grade 1 endometrial cancers and is found most commonly in MSS tumors. MSI-H is also present at significantly higher rates in recurrent cases. These markers may be useful for prognostic risk stratification and adjuvant therapy decision-making in this otherwise low-risk population.

Primary Nonanaplastic Peripheral Natural Killer/T-Cell Lymphoma in Pediatric Patients-An Unusual Distribution Pattern of Subtypes.

Peripheral NK/T-cell lymphoma (PNKTCL) represents a group of uncommon diagnoses for children in Western countries, and studies have often necessitated multiple institutions to assemble enough cases. We retrospectively analyzed 11 cases of nonanaplastic PNKTCL in children over 19 years at our institution with comparison to several published large multi-institutional studies. Patients included 9 males and 2 females of white (5), Native American (3), and Hispanic (3) background with 6 cases of extranodal NK/T-cell lymphoma, nasal type (EN-NKTL, 54.6%), 3 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS, 27.2%), and 2 cases of systemic Epstein-Barr virus (EBV)-positive T-cell lymphoma of childhood (18.2%). Compared to the literature, our institution exceeded in frequency of total nonanaplastic PNKTCL (4.8% vs 0.9%-1.6%) with lesser relative incidence of PTCL-NOS (27.2% vs 42.9%-66.7%) and greater relative incidence of EN-NKTL (54.6% of cases vs 12.5%-47.6%), which significantly exceeded the literature's rate for Western institutions (13.5%). Potential influencing factors include population structure approximating those of non-Western countries with high EN-NKTL prevalence and the predisposition for EBV infection in this demography. These data suggest an uneven distribution of nonanaplastic PNKTCL in Western countries, and differential diagnoses may differ depending on practice location and associated patient population.

Intracranial Involvement by Plasma Cell Neoplasms.

OBJECTIVES: Intracranial plasma cell neoplasms (PCNs) arising from the skull, dura, or brain parenchyma are rare tumors and there is only a limited experience in the literature with these lesions. METHODS: We performed a retrospective clinicopathologic study of fourteen cases of intracranial PCN at our institution encountered over a 26-year-period. RESULTS: The fourteen patients ranged in age from 30-74 years (median 66 years) and included seven males. For eight patients, their intracranial lesions were the initial presentation of multiple myeloma (MM). Three patients had prior history of MM; their intracranial tumors showed blastic plasma cell morphology, and all three died secondary to MM. The remaining three patients did not or have not developed MM. CONCLUSIONS: PCNs rarely arise in the intracranial compartment. Intracranial PCN may be the initial presentation of MM. Anecdotally, blastic morphology appears to manifest more aggressive behavior.

Intracranial involvement of posttransplant lymphoproliferative disorder multiple myeloma.

We report a 61-year-old man with intracranial multiple myeloma (MM) presenting as a posttransplant lymphoproliferative disorder (PTLD) following a kidney transplant. Two months after his transplant, the man developed acute rejection with Epstein-Barr virus (EBV) viremia, requiring aggressive immunosuppression. Twenty months following transplantation, the patient presented with multiple neurologic deficits. Imaging revealed numerous lytic lesions in the skull, most conspicuously a 4.1cm right frontal skull mass with prominent intracranial extension. Histologic sections of the frontal bone lesion showed sheets of atypical plasma cells that were positive for CD138 and kappa immunoglobulin light chains. Chromogenic in situ hybridization for EBV-encoded small RNA was also positive. Plasma cell neoplasms, either as MM or a plasmacytoma, are one of the least common forms of PTLD, and their rarity limits the possibility of major studies to detail their behavior. Most often seen after renal transplantation, the majority are EBV-driven, similarly to other PTLD. While studies have demonstrated several risk factors, behavior and optimal management of PTLD plasma cell neoplasms are unknown. Plasma cell neoplasms affect the nervous system in a variety of ways but rarely via intracranial disease. MM usually presents initially with several classic signs and symptoms, but our patient's presentation was typical of a localized brain tumor with generalized and focal gross neurologic defects.