GATA3 is a reliable diagnostic marker for NBs not only in scant/limited surgical specimens but also in cytologic samples, including air-dried touch imprints, which have previously been undescribed for this marker. Cancer Cytopathol 2017;125:940-6. © 2017 American Cancer Society.

Epstein-Barr virus (EBV)-positive plasmacytoma is a rare plasma cell neoplasm. It remains unclear whether EBV-positive plasmacytoma represents a distinct entity or a variant of plasmacytoma. It shares morphologic features with plasmablastic lymphoma (PBL) and may cause diagnostic uncertainty. To better understand EBV-positive plasmacytoma and explore diagnostic criteria, this study describes 19 cases of EBV-positive plasmacytoma, compared with 27 cases of EBV-negative plasmacytoma and 48 cases of EBV-positive PBL. We reviewed the clinicopathologic findings and performed immunohistochemistry, in situ hybridization for EBV, fluorescence in situ hybridization for MYC, and next-generation sequencing. We found that 63.2% of patients with EBV-positive plasmacytoma were immunocompromised. Anaplastic features were observed in 7/19 cases. MYC rearrangement was found in 25.0% of them, and extra copies of MYC in 81.3%. EBV-positive and EBV-negative plasmacytomas possessed similar clinicopathologic features, except more frequent cytologic atypia, bone involvement and MYC aberrations in the former group. The survival rate of patients with EBV-positive plasmacytoma was comparable to that of patients with EBV-negative plasmacytoma. In comparison to PBL, EBV-positive plasmacytoma is less commonly associated with a “starry-sky” appearance, necrosis, absence of light chain expression, and a high Ki67 index (>75%). The most recurrently mutated genes/signaling pathways in EBV-positive plasmacytoma are epigenetic regulators, MAPK pathway, and DNA damage response, while the most frequently reported mutations in PBL are not observed. Collectively, EBV-positive plasmacytoma should be regarded as a biological variant of plasmacytoma. Thorough morphologic examination remains the cornerstone for distinguishing EBV-positive plasmacytoma and PBL, and molecular studies can be a valuable complementary tool.

Primary cutaneous marginal zone lymphoproliferative disorder (PCMZL) and primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+ TLPD) are indolent lymphoproliferative disorders. However, cases with overlapping features can be challenging. We identified 56 CD4+ TLPD and 38 PCMZL cases from our pathology archives. Clinical, morphologic, and immunophenotypic features were reviewed. Polymerase chain reaction for immunoglobulin (IG) and T-cell receptor gamma (TRG) gene rearrangements were analyzed. Next-generation sequencing studies were performed on 26 cases with adequate material, 19 with CD4+ TLPD, and 7 with PCMZL. CD4+ TLPD presented mostly (91%) as solitary lesions, located in the head and neck area (64%), while PCMZL occurred mostly in the upper extremity (47%) and trunk (34%). Lesions were sometimes multiple (40%) and recurrences (67%) were more common. Cases of PCMZL had an increase in reactive CD3+ T cells, with frequent programmed cell death protein 1 expression, whereas cases of CD4+ TLPD often contained abundant reactive B cells. Twenty-five cases were identified as having overlapping features: 6 cases of PCMZL were clonal for both IG and TRG; 11 cases of CD4+ TLPD were clonal for IG and TRG and 6 cases of CD4+ TLPD had light chain–restricted plasma cells. By next-generation sequencing, 23 variants were detected in 15 genes, with PCMZL more likely to show alterations, most commonly affecting TNFAIP3 and FAS, altered in 5 cases. Both entities have an indolent clinical course with response to conservative therapy and management, and warrant interpretation as a lymphoproliferative disorder rather than overt lymphoma.

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Follicular dendritic cell sarcoma (FDCS) is recognized as a diagnostically challenging neoplasm requiring rigorous exclusion of more common entities and high index of suspicion for diagnosis. Here, we report an aggressive case of FDCS arising in the mediastinum, which due to sampling limitations and the inherent difficulty of diagnosis required extensive workup with multiple samples prior to definitive classification. The patient was a 35-year-old woman who presented with progressive dyspnea and mediastinal mass on imaging studies. The initial sampling of the lesion had histologic features raising consideration of FDCS, but was too limited to allow definitive diagnosis, while progressing rapidly enough to require administration of chemotherapy even prior to classification. Repeat samples obtained via fine-needle aspiration and bronchoscopy enabled the diagnosis of FDCS, and high-throughput sequencing revealed apparently pathogenic NF2 mutations previously not reported in this disease. Unfortunately, the patient died of widely metastatic disease, which we comprehensively documented at autopsy. Together, these observations provide previously unreported insights into the end stage of this disease and experience relevant to its prospective recognition and workup.

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