A 54-year-old female patient was admitted to the hospital due to a headache lasting for more than 10 days. Cranial computed tomography (CT), as well as regular magnetic resonance imaging (MRI) in combination with contrast-enhanced MRI, showed an irregular mass measuring 31×27×20 mm in the right temporal lobe. The contrast-enhanced scan was unevenly enhanced, and a large area of non-enhanced edema involving the basal ganglia was observed. The right lateral ventricle and third ventricle were compressed, and the midline structure was shifted to the left by approximately 9.4 mm. Additionally, the presence of right temporal lobe lymphoma or metastases was assessed (Fig. 1). Cranial functional magnetic resonance spectroscopy (MRS) indicated that the right temporal lobe tumor had increased Cho, a decreased Cr peak, a decreased NAA peak, and a maximum Ch/NAA ratio of 4.58. Additionally, MRS indicated that the tumor in the right temporal lobe was prone to malignancy. The PET-CT data indicated that, characteristic of primary brain tumors, the right temporoparietal space-occupying lesions had increased metabolism (SUVmax 25) and large surrounding edema. No obvious areas of increased metabolism were found. Serology assessments revealed that the patient was HIV and HHV-8 negative. Intraoperatively, the tumor was located on the deep surface of the right temporal lobe. The tumor was solid, translucent jelly-like, with clear borders, no capsule, minimal vasculature, and possessed a soft texture. The patient's and family's history was unremarkable.
Gross pathological examination revealed an area of broken gray-white tissue (2.5×2×1 cm) with partial hyperemia, no capsule, and gray-white matter on the cut surface. Under low magnification, the brain tissue was diffusely infiltrated and severely damaged by many large lymphoid cells and no lymphoid follicle structures were observed (Fig. 2A). Additionally, local tumor interstitial microvascular proliferation, tumor cell arrangement around the blood vessels (Fig. 2B), and tumor cell infiltration of the blood vessels intracavity were noted. Under high magnification, the tumor cells were medium to large, round or oval, possessed clear nuclear membranes, displayed different nuclear staining characteristics, were variably vacuolated or possessing of irregular mass, exhibited nucleoli, and had 1 to 3 nucleoli of central or near nuclear membranes, cytoplasmic dichromatic or basophilic cells, centroblast-like and immunoblastic-like cells, and pathological mitotic cells are shown (Fig. 2C). From these morphological data, lymphoma was diagnosed, specifically favoring DLBCL.
Immunohistochemical assays identified the presence of large lymphoid cells by LCA+++, CD79a+ (Fig. 3A), PAX-5+ (Fig. 3B), MUM1+ (Fig. 3C), CD3-, and CD5- staining that, together, are indicative of B cells involvement. Furthermore, the patient’s tissue was CD10-, Bcl-6+, and MUM1+, indicative that the cells did not originate from a germinal center. CyclinD1-, CD5-, SOX-11-, and Bcl-2- staining data indicated that mantle cells and follicular cells likely did not contribute to the current phenotype. The EMA, GFAP, IDH1, P53, O1igo-2, S100, Syn, and CgA marks were all negative, thus excluding central nervous epithelial tumors such as astrocytoma and oligodendroglioma from consideration. Together, due to these data in combination with Ki-67 expression (90% positivity) (Fig. 3D), which is suggestive of active proliferation, the patient was diagnosed with DLBCL.
CD20 and CD21 staining of the tissues was negative. Initially, this result was considered to be a technical error that was introduced during the immunohistochemical analyses. However, upon repetition of the assay, and including a robust positive control, the results showed that the tissue remained CD20 negative (Fig. 3E-F) (the positive control was strongly positive (Fig. 3G)). Additionally, the reactive lymphocytes of the surrounding brain tissue between the tumor were CD20 positive (Fig. 3H), which further excluded any false negatives that may have been present in the tissue-embedded wax block. Combined with morphological features and reliable immunohistochemical indicators, a definitive diagnosis of CD20-negative DLBCL was made.
To clarify the specific lymphoma type, additional immune indicators were assessed. The ALK, CD138, CD38, and EBER/ISH markers were all negative. Additionally, the Bcl-6 and EMA markers came back positive and negative, respectively. Laboratory serology revealed that the patient was HIV and HHV-8 negative. From these observations, the possibility that the current case was EBV-positive LBCL with plasmacytoid differentiation, primary effusion lymphoma (PEL), plasmablastoma (PBL), ALK+ LBCL, or HHV8+ DLBCL, NOS was dismissed. Combined with HE morphological features, these serological results are not consistent with anaplastic DLBCL. Additionally, the patient's medical history was well recorded and no history of tumor and drug use (including rituximab) was present. Therefore, CD20-negative DLBCL with drug-induced CD20 antigen loss was excluded. Next-generation sequencing (NGS) was then used to detect 101 genes related to lymphoma. Of these genes, 11 gene mutations (Table 1), including BTG2, ITPKB, TET2, FAT1, PIM1, CARD11, KMT2C, NOTCH1, KMT2D, SOCS1, and BCORL1 were noted.
Together, these data in combination with the patient's clinical history laboratory tests, HE morphological features, reliable immunohistochemical results, and genetic testing results, the diagnosis was CD20-negative DLBCL of the right temporal lobe. The specific type was noted as being unclassifiable/unclassified. After the patient was diagnosed with lymphoma, he was transferred to the cancer hospital for CHOP chemotherapy. The patient’s condition was stable and they were followed up closely.