Double-hit lymphoma (DHL) formerly referred to high-grade B-cell lymphoma with concurrent MYC and BCL2 or BCL6 rearrangements, however, the updated 2022 World Health Organization Classification (5th edition online) excludes those with MYC and BCL 6 rearrangements from the high-grade category. DHL confined to the central nervous system (CNS), known as double-hit primary CNS lymphoma (DH-PCNSL), is rare with poorly understood clinical features. Here, we report a case of a 64-year-old man with multiple brain tumors diagnosed with DH-PCNSL who showed bone marrow (BM) infiltration early in the clinical course. The histological diagnosis was high-grade B-cell lymphoma with MYC and BCL6 rearrangements. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal accumulation except in the CNS. The patient received whole-brain radiotherapy following the failure of high-dose methotrexate. After completion of radiotherapy, the patient developed thrombocytopenia, and BM biopsy showed infiltration of DHL cells, which were not detected by repeated FDG-PET. This is the first report of DH-PCNSL where identical gene rearrangements were confirmed in both the resected CNS tumor and BM tissue. Patients with DH-PCNSL require careful follow-up because they may be at a potential risk of BM infiltration, which may be undetectable by FDG-PET, particularly early in the disease course.

Primary ovarian non-Hodgkin lymphoma is a rare lymphoma that is often associated with diagnostic delays, initial misdiagnosis, and inappropriate management. We report a case of ovarian diffuse large B-cell lymphoma (DLBCL) in a young female who initially presented with generalized fatigue, lower abdominal discomfort, and 40 pounds of unintentional weight loss. She subsequently had a computed tomography of abdomen done that showed fatty liver, hepatomegaly, and a left heterogeneous ovarian mass measuring about 4 × 4.2 cm. Transvaginal ultrasound was also done that showed a heterogeneous solid left adnexal mass measuring 7.4 × 5.6 × 6.6 cm. She subsequently had a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Immunohistochemistry (IHC) showed the malignant cells expressing PAX5, CD20, and BCL2 with a Ki-67 proliferation index greater than 90%. The cells were negative for AE1/AE3, S100, CD30, and cyclin D1. Aggressive B-cell lymphoma fluorescence in situ hybridisation (FISH) panel was positive for rearrangement of BCL6 and MYC, with no evidence of BCL2 rearrangement, consistent with a double-hit high-grade B-cell lymphoma. Immunohistochemistry for BCL6 and MU M1 showed positive staining in the malignant cells. CD10 was negative. The staining profile was consistent with nongerminal center B-cell-like type of DLBCL. Ovarian lymphoma is a very rare entity; the presence of an enlarged ovarian tumor should raise the suspicion of ovarian lymphoma, and our case also emphasizes on the use of IHC markers in diagnosing the ovarian DLBCL.

BACKGROUND: Double-hit lymphoma is a highly aggressive B-cell lymphoma that is genetically characterized by rearrangements of MYC and BCL2 and/or BCL6. Lymphoma is often accompanied by atypical systemic symptoms similar to physiological changes during pregnancy and is often ignored. Herein, we describe a gravid patient with high-grade B-cell lymphoma with a MYC and BCL-2 gene rearrangement involving multiple parts of the body.
METHODS: A 32-year-old female, gestational age 22+5 wk, complained of abdominal distension, chest tightness and limb weakness lasting approximately 4 wk, and ovarian tumors were found 14 d ago. Auxiliary examinations and a trimanual gynecologic examination suggested malignant ovarian tumor and frozen pelvis. Coupled with rapid progression, severe compression symptoms of hydrothorax, ascites and moderate anemia, labor was induced. Next, biopsy and imaging examinations showed high-grade B-cell lymphoma with a MYC and BCL-2 gene rearrangement involving multiple parts of the body. She was referred to the Department of Oncology and Hematology for chemotherapy. Because of multiple recurrences after complete remission, chemotherapy plans were continuously adjusted. At present, the patient remains in treatment and follow-up.
CONCLUSIONS: The early detection and accurate diagnosis of lymphoma during pregnancy can help expedite proper multidisciplinary treatment to delay disease progression and decrease the mortality rate.

暂无摘要。

Most commonly, histologic transformation (HT) from follicular lymphoma (FL) manifests as a diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Less frequently, HT may result in a high-grade B-cell lymphoma (HGBL) with MYC and B-cell lymphoma protein 2 (BCL2) and/or BCL6 gene rearrangements, also known as \"double-hit\" or \"triple-hit\" lymphomas. In the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms, the category B-cell lymphoma, unclassifiable was eliminated due to its vague criteria and limiting diagnostic benefit. Instead, the WHO introduced the HGBL category, characterized by MYC and BCL2 and/or BCL6 rearrangements. Cases that present as an intermediate phenotype of DLBCL and Burkitt lymphoma (BL) will fall within this HGBL category. Very rarely, HT results in both the intermediate DLBCL and BL phenotypes and exhibits lymphoblastic features, in which case the WHO recommends that this morphologic appearance should be noted. In comparison with de novo patients with DLBCL, NOS, those with MYC and BCL2 and/or BCL6 gene rearrangements have a worse prognosis. A 63-year-old woman presented with left neck adenopathy. Laboratory assessments, including complete blood count, complete metabolic panel, serum lactate dehydrogenase, and β2-microglobulin, were all normal. A whole-body computerized tomographic (CT) scan revealed diffuse adenopathy above and below the diaphragm. An excisional node biopsy showed grade 3A nodular FL. The Ki67 labeling index was 40% to 50%. A bone marrow biopsy showed a small focus of paratrabecular CD20+ lymphoid aggregates. She received 6 cycles of bendamustine (90 mg/m2 on days +1 and +2) and rituximab (375 mg/m2 on day +2), with each cycle delivered every 4 weeks. A follow-up CT scan at completion of therapy showed a partial response with resolution of axillary adenopathy and a dramatic shrinkage of the large retroperitoneal nodes. After 18 months, she had crampy abdominal pain in the absence of B symptoms. Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with CT (18F-FDG PET/CT) scan showed widespread adenopathy, diffuse splenic involvement, and substantial marrow involvement. Biopsy of a 2.4-cm right axillary node (SUVmax of 16.1) showed involvement by grade 3A FL with a predominant nodular pattern of growth. A bone marrow biopsy once again showed only a small focus of FL. She received idelalisib (150 mg twice daily) and rituximab (375 mg/m2, monthly) beginning May 2015. After 4 cycles, a repeat CT scan showed a complete radiographic response. Idelalisib was subsequently held while she received corticosteroids for immune-mediated colitis. A month later, she restarted idelalisib with a 50% dose reduction. After 2 weeks, she returned to clinic complaining of bilateral hip and low lumbar discomfort but no B symptoms. A restaging 18F-FDG PET/CT in January 2016 showed dramatic marrow uptake. A bone marrow aspirate showed sheets of tumor cells representing a spectrum from intermediate-sized cells with lymphoblastic features to very large atypical cells with multiple nucleoli. Two distinct histologies were present; one remained consistent with the patient\'s known FL with a predominant nodular pattern and the other consistent with HT (the large atypical cells expressed PAX5, CD10, BCL2, and c-MYC and were negative for CD20, MPO, CD34, CD30, and BCL6). Focal areas showed faint, heterogeneous expression of terminal deoxynucleotidyl transferase best seen on the clot section. Ki67 proliferation index was high (4+/4). Fluorescence in situ hybridization analysis showed 2 populations with MYC amplification and/or rearrangement and no evidence of BCL6 rearrangement; a karyotype analysis showed a complex abnormal female karyotype with t(14;18) and multiple structural and numerical abnormalities. She started dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin with concomitant prophylactic intrathecal methotrexate and cytarabine. She had but a short-lived response before dying in hospice from progressive lymphoma. Whether idelalisib could provide a microenvironment for selection of more aggressive clones needs to be addressed. Our patient\'s clinical course is confounded by the incorporation of idelalisib while being further complicated by the complexity of HT and the mechanisms in which first-line chemotherapy regimens affect double-hit lymphoma.