Storylines of family medicine II: foundational building blocks-context, community and health.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'II: foundational building blocks-context, community and health', authors address the following themes: 'Context-grounding family medicine in time, place and being', 'Recentring community', 'Community-oriented primary care', 'Embeddedness in practice', 'The meaning of health', 'Disease, illness and sickness-core concepts', 'The biopsychosocial model', 'The biopsychosocial approach' and 'Family medicine as social medicine.' May readers grasp new implications for medical education and practice in these essays.

TB-free Ebeye: Results from integrated TB and noncommunicable disease case finding in Ebeye, Marshall Islands.

Background: Tuberculosis (TB) incidence rates in the Republic of the Marshall Islands are among the highest in the world, 480/100,000 in 2017. In response, the Health Ministry completed islandwide screening in Ebeye Island in 2017. Methods: Participants were interviewed to obtain TB history, exposures, and symptoms. TB assessment included chest radiography with sputum collection for GeneXpert® MTB-RIF if indicated. TB diagnosis was made by consensus of visiting TB experts. Participants were also screened for Hansen's disease (HD) and diabetes mellitus (DM). For persons aged ≥21 years, blood pressure, cholesterol, and blood glucose were assessed. Results: A total of 5,166 persons (90.0 % of target population) completed screening leading to the identification of 39 new cases of TB (755/100,000) and 14 persons with HD (270/100,000). DM was detected in 1,096 persons (27 %), including in 351 persons not previously diagnosed. The rate of hypertension was 61 % and of hypercholesterolemia was 15 %. New or prevalent TB diagnosis was associated with newly diagnosed or history of DM (aOR 4.68, 2.15-10.20). Conclusions: In Ebeye, an integrated TB screening campaign found TB, HD, DM, and hypertension. TB and DM were strongly associated.

Chromogenic in situ hybridization reveals specific expression pattern of long non-coding RNA DRAIC in formalin-fixed paraffin-embedded specimen.

Long non-coding RNA (lncRNA) plays an important role in the regulation of gene expression in normal and cancer cells. We previously discovered a novel tumor-suppressive lncRNA, DRAIC, in prostate cancer cells. Subsequent studies have demonstrated that DRAIC is dysregulated in various malignancies and exhibits a tumor-suppressive or pro-oncogenic function. However, details regarding its expression pattern in normal and cancerous tissues remain largely unknown. In this study, we performed chromogenic in situ hybridization (CISH) using RNAscope technology to assess DRAIC expression in formalin-fixed paraffin-embedded (FFPE) specimens. In the neuroendocrine-differentiated cancer cell line VMRC-LCD, CISH revealed a diffuse localization of DRAIC in the cytoplasm as well as specific accumulation in the nuclear compartment. DRAIC expression was comprehensively analyzed using tissue microarrays containing 89 normal and 155 tumor tissue samples. DRAIC was weakly expressed in normal epithelial cells of the colon, bronchiole, kidney, prostate, and testis. Conversely, DRAIC was moderately to highly expressed in some cancer tissues, including prostate adenocarcinoma, invasive ductal carcinoma of the breast, neuroendocrine carcinoma of the esophagus, lung adenocarcinoma, and small cell lung carcinoma. While DRAIC knockdown did not affect VMRC-LCD cellular viability and invasive ability, gene expression related to the neuroendocrine and cancer-related pathways was altered. Our expression analysis revealed the specific expression pattern of DRAIC in normal and cancerous FFPE tissues. The results presented here may lead to the elucidation of additional novel functions of DRAIC.

SEGA-like circumscribed astrocytoma in a non-NF1 patient, harboring molecular profile of GBM. A case report.

Subependymal giant cell astrocytoma (SEGA) is a low-grade periventricular tumor that is closely associated with tuberous sclerosis complex (TSC). SEGA typically arises during the first two decades of life and rarely arises after the age of 20-25 years. Nevertheless, it has also been reported that glioma histologically resembling SEGA, so-called SEGA-like astrocytoma, can arise in neurofibromatosis type 1 (NF1) patients, even in the elderly. Herein, we report a case of SEGA-like circumscribed astrocytoma arising in the lateral ventricle of a 75-year-old woman. Whole-exome sequencing revealed a somatic variant of NF1. Methylation array analysis led to a diagnosis of "methylation class glioblastoma, IDH-wildtype, mesenchymal-type (GBM, MES)" with a high calibrated score (0.99). EGFR amplification, CDKN2A/B homozygous deletion, chromosomal +7/-10 alterations, and TERT promoter mutation, typical molecular abnormalities usually found in GBM, were also observed. While most reported cases of SEGA-like astrocytoma have arisen in NF1 patients, the patient was neither TSC nor NF1. Near total removal was accomplished with endoscopic cylinder surgery. At the 36-month follow-up, there was no tumor recurrence without adjuvant therapies. This clinical behavior did not match GBM. SEGA-like astrocytoma of the elderly is rare, and this is the oldest case reported so far. In addition, high-grade molecular features found in circumscribed tumor remain unclear. Further investigations among larger series are needed for clarifying the underlying molecular mechanisms.

Early detection of genotoxic hepatocarcinogens in rats using γH2AX and Ki-67: prediction by machine learning.

Direct DNA double-strand breaks result in phosphorylation of H2AX, a variant of the histone H2 protein. Phosphorylated H2AX (γH2AX) may be a potential indicator in the evaluation of genotoxicity and hepatocarcinogenicity. In this study, γH2AX and Ki-67 were detected in the short-term responses (24 h after chemical administration) to classify genotoxic hepatocarcinogens (GHs) from non-GH chemicals. One hundred and thirty-five 6-week-old Crl: CD(SD) (SPF) male rats were treated with 22 chemicals including 11 GH and 11 non-GH, sacrificed 24 h later, and immunostained with γH2AX and Ki-67. Positivity rates of these markers were measured in the 3 liver ZONEs 1-3; portal, lobular, and central venous regions. These values were input into 3 machine learning models-Naïve Bayes, Random Forest, and k-Nearest Neighbor to classify GH and non-GH using a 10-fold cross-validation method. All 11 and 10 out of 11 GH caused significant increase in γH2AX and Ki-67 levels, respectively (P < .05). Of the 3 machine learning models, Random Forest performed the best. GH were identified with 95.0% sensitivity (76/80 GH-treated rats), 90.9% specificity (50/55 non-GH-treated rats), and 90.0% overall correct response rate using γH2AX staining, and 96.2% sensitivity (77/80), 81.8% specificity (45/55), and 90.4% overall correct response rate using Ki-67 labeling. Random Forest model using γH2AX and Ki-67 could independently predict GH in the early stage with high accuracy.

Utility of cerebrospinal fluid liquid biopsy in distinguishing CNS lymphoma from cerebrospinal infectious/demyelinating diseases.

BACKGROUND: Distinguishing between central nervous system lymphoma (CNSL) and CNS infectious and/or demyelinating diseases, although clinically important, is sometimes difficult even using imaging strategies and conventional cerebrospinal fluid (CSF) analyses. To determine whether detection of genetic mutations enables differentiation between these diseases and the early detection of CNSL, we performed mutational analysis using CSF liquid biopsy technique. METHODS: In this study, we extracted cell-free DNA from the CSF (CSF-cfDNA) of CNSL (N = 10), CNS infectious disease (N = 10), and demyelinating disease (N = 10) patients, and performed quantitative mutational analysis by droplet-digital PCR. Conventional analyses were also performed using peripheral blood and CSF to confirm the characteristics of each disease. RESULTS: Blood hemoglobin and albumin levels were significantly lower in CNSL than CNS infectious and demyelinating diseases, CSF cell counts were significantly higher in infectious diseases than CNSL and demyelinating diseases, and CSF-cfDNA concentrations were significantly higher in infectious diseases than CNSL and demyelinating diseases. Mutation analysis using CSF-cfDNA detected MYD88L265P and CD79Y196 mutations in 60% of CNSLs each, with either mutation detected in 80% of cases. Mutual existence of both mutations was identified in 40% of cases. These mutations were not detected in either infectious or demyelinating diseases, and the sensitivity and specificity of detecting either MYD88/CD79B mutations in CNSL were 80% and 100%, respectively. In the four cases biopsied, the median time from collecting CSF with the detected mutations to definitive diagnosis by conventional methods was 22.5 days (range, 18-93 days). CONCLUSIONS: These results suggest that mutation analysis using CSF-cfDNA might be useful for differentiating CNSL from CNS infectious/demyelinating diseases and for early detection of CNSL, even in cases where brain biopsy is difficult to perform.

Future Perspective for ALK-Positive Anaplastic Large Cell Lymphoma with Initial Central Nervous System (CNS) Involvement: Could Next-Generation ALK Inhibitors Replace Brain Radiotherapy for the Prevention of Further CNS Relapse?

Central nervous system (CNS) involvement in anaplastic large cell lymphoma (ALCL) at diagnosis is rare and leads to poor prognosis with the use of the standard ALCL99 protocol alone. CNS-directed intensive chemotherapy, such as an increased dose of intravenous MTX, increased dose of dexamethasone, intensified intrathecal therapy, and high-dose cytarabine, followed by cranial irradiation, has been shown to improve survival in this population. In this paper, the authors describe a 14-year-old male with an intracranial ALCL mass at onset who received CNS-directed chemotherapy followed by 23.4 Gy of whole-brain irradiation. After the first systemic relapse, the CNS-penetrating ALK inhibitor, alectinib, was applied; it has successfully maintained remission for 18 months without any adverse events. CNS-penetrating ALK inhibitor therapy might prevent CNS relapse in pediatric ALK-positive ALCL. Next-generation ALK inhibitors could be introduced as a promising treatment option, even for primary ALCL with CNS involvement, which could lead to the omission of cranial irradiation and avoid radiation-induced sequalae. Further evidence of CNS-penetrating ALK inhibitor combined therapy for primary ALK-positive ALCL is warranted to reduce radiation-induced sequalae in future treatments.

Influence of agent's self-disclosure on human empathy.

As AI technologies progress, social acceptance of AI agents, including intelligent virtual agents and robots, is becoming even more important for more applications of AI in human society. One way to improve the relationship between humans and anthropomorphic agents is to have humans empathize with the agents. By empathizing, humans act positively and kindly toward agents, which makes it easier for them to accept the agents. In this study, we focus on self-disclosure from agents to humans in order to increase empathy felt by humans toward anthropomorphic agents. We experimentally investigate the possibility that self-disclosure from an agent facilitates human empathy. We formulate hypotheses and experimentally analyze and discuss the conditions in which humans have more empathy toward agents. Experiments were conducted with a three-way mixed plan, and the factors were the agents' appearance (human, robot), self-disclosure (high-relevance self-disclosure, low-relevance self-disclosure, no self-disclosure), and empathy before/after a video stimulus. An analysis of variance (ANOVA) was performed using data from 918 participants. We found that the appearance factor did not have a main effect, and self-disclosure that was highly relevant to the scenario used facilitated more human empathy with a statistically significant difference. We also found that no self-disclosure suppressed empathy. These results support our hypotheses. This study reveals that self-disclosure represents an important characteristic of anthropomorphic agents which helps humans to accept them.

Three-Dimensional Amide Proton Transfer-Weighted Imaging for Differentiating between Glioblastoma, IDH-Wildtype and Primary Central Nervous System Lymphoma.

Distinguishing primary central nervous system lymphoma (PCNSL) from glioblastoma, isocitrate dehydrogenase (IDH)-wildtype is sometimes hard. Because the role of operation on them varies, accurate preoperative diagnosis is crucial. In this study, we evaluated whether a specific kind of chemical exchange saturation transfer imaging, i.e., amide proton transfer-weighted (APTw) imaging, was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. A total of 14 PCNSL and 27 glioblastoma, IDH-wildtype cases were evaluated. There was no significant difference in the mean APTw signal values between the two groups. However, the percentile values from the 1st percentile to the 20th percentile APTw signals and the width1-100 APTw signals significantly differed. The highest area under the curve was 0.796, which was obtained from the width1-100 APTw signal values. The sensitivity and specificity values were 64.3% and 88.9%, respectively. APTw imaging was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. To avoid unnecessary aggressive surgical resection, APTw imaging is recommended for cases in which PCNSL is one of the differential diagnoses.

Trends of International Electives in Medical Education Undergraduates in Japan.

Increasing numbers of medical students participate in international electives. However, this recent trend has yet to be examined in non-Western high-income countries such as Japan. The aim of this study is to assess recent trends in Japan, and to suggest ways in which those trends might be influenced. A retrospective cross-sectional analysis of responses to an 8-item questionnaire sent in August 2019 to 82 medical schools in Japan is reported. The responses were received in September 2019. Narrative responses were obtained regarding rationales for exchange programs, participant feedback, and challenges encountered. Responses were translated into English and categorized into themes. Of 82 Japanese medical schools, 56 (68%) responded to the questionnaire. Both the number of incoming and outgoing exchange students had increased steadily over the preceding 3-year period. The leading destinations for Japanese students were the United States (30%), other Asian (36%), and European countries (24%). Narrative responses reveal different rationales from those reported by medical schools in Western high-income countries. Only a few Japanese students chose low or middle-income countries as their destinations, as opposed to the trend seen in Western high-income countries. The reported challenges encountered by the exchange programs may provide insights for improvement. Exchanges have been greatly affected by the coronavirus disease 2019 pandemic. The results can serve as pre-pandemic baseline data and should promote further international collaboration for medical education under current circumstances.

DNA methylation array analysis for diffuse leptomeningeal glioneuronal tumor with conspicuous hypothalamic mass. A case report.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare glioneuronal neoplasm newly included in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. Owing to the wide spectrum of its histopathological and radiological features, accurate diagnosis can be challenging. Recently, molecular testing including DNA methylation array has been introduced with the possibility of improving diagnostic accuracy and contributing to the subtyping especially for brain tumors with ambiguous histology. Two molecularly distinct subtypes of DLGNT have been reported: methylation class-1 (MC-1) with an indolent clinical course and MC-2, the latter aggressive. Herein, we report a case of a 14-year-old girl with a conspicuous hypothalamic mass lesion and diffuse leptomeningeal enhancement on magnetic resonance imaging. Biopsy specimens obtained from the hypothalamic lesion endoscopically were mainly composed of oligodendrocyte-like cells. However, it was difficult to make a definite diagnosis from these non-specific histological findings. Thus, DNA methylation array analysis was performed additionally by using formalin-fixed, paraffin-embedded tissue, resulting in a diagnosis of "MC-1 subtype of DLGNT" with a high calibrated score (0.99). Consequently, she was treated conservatively, with neither progression of the tumor nor aggravation of symptoms for the next 12 months. It was concluded that DNA methylation array analysis for DLGNT, a rare glioneuronal tumor, could be a powerful tool not only for accurate diagnosis but also decision-making in selecting the best treatment.

Totally laparoscopic resection using delta-shaped anastomosis of jejunal leiomyosarcoma with intussusception at the angle of Treitz: a case report.

BACKGROUND: A leiomyosarcoma of the gastrointestinal tract is extremely rare. We report a case of jejunal leiomyosarcoma with intestinal intussusception at the angle of Treitz that was successfully treated with laparoscopic resection followed by intracorporeal reconstruction using a delta-shaped anastomosis. CASE PRESENTATION: A 54-year-old man was referred to our hospital due to fatigue and loss of appetite. Blood tests showed anemia. Enteroscopy and subsequent enterography using meglumine sodium amidotrizoate showed easily hemorrhagic tumor (10 cm in diameter) in the jejunum just beyond the angle of Treitz. Contrast-enhanced computed tomography revealed jejunojejunal intussusception. Histopathological examination of a biopsy specimen revealed a leiomyosarcoma. Laparoscopic resection of the tumor without reduction of the intussusception was performed. The resected line of the proximal intestine was very close to the ligament of Treitz in the present case. Intracorporeal jejunojejunostomy was completed using a delta-shaped anastomosis, wherein anastomosis was performed between the posterior walls of the proximal and distal jejunums after minimal mobilization around the ligament of Treitz. The patient's postoperative course was uneventful, and he was discharged at 10 days postoperatively. No recurrence has been observed within 2 years after surgery. CONCLUSIONS: We present a case in which a totally laparoscopic surgery for leiomyosarcoma located at the angle of Treitz with jejunojejunal intussusception was performed successfully.

Morphologic Analysis of M2 Macrophage in Glioblastoma: Involvement of Macrophage Extracellular Traps (METs).

Macrophages are classified into two phenotypes, M1 and M2, based on their roles. M2 macrophages suppress inflammation and increase in proportion to the malignancy of brain tumors. Recently, macrophage extracellular traps (METs), which change into a network, have been reported as a unique form of macrophage cell death. In this study, immunohistochemical analysis of macrophages in METs in human glioblastoma was performed. To distinguish between M1 and M2 macrophages, multiple immunostainings with Iba1 combined with CD163 or CD204 were performed. M2 macrophages were present in small amounts in normal and borderline areas but showed an increasing trend as they shifted to tumor areas, and most of them were the activated- or phagocytic-type. We also successfully detected METs coexisting with fibrin and lactoferrin near the border between the tumor and necrotic area. M2 macrophages not only suppressed inflammation but also were involved in the formation of METs. This study found that M2 macrophages play various roles in unstable situations.

Intraoperative Real-Time Near-Infrared Image-Guided Surgery to Identify Intracranial Meningiomas via Microscope.

Meningiomas are a common pathology in the central nervous system requiring complete surgical resection. However, in cases of recurrence and post-irradiation, accurate identification of tumor remnants and a dural tail under bright light remains challenging. We aimed to perform real-time intraoperative visualization of the meningioma and dural tail using a delayed-window indocyanine green (ICG) technique with microscopy. Fifteen patients with intracranial meningioma received 0.5 mg/kg ICG a few hours before observation during the surgery. We used near-infrared (NIR) fluorescence to identify the tumor location. NIR fluorescence could visualize meningiomas in 12 out of 15 cases. Near-infrared visualization during the surgery ranged from 1 to 4 h after the administration of ICG. The mean signal-to-background ratio (SBR) of the intracranial meningioma in delayed-window ICG (DWIG) was 3.3 ± 2.6. The ratio of gadolinium-enhanced T1 tumor signal to the brain (T1BR) (2.5 ± 0.9) was significantly correlated with the tumor SBR (p = 0.016). K trans , indicating blood-brain barrier permeability, was significantly correlated with tumor SBR (p < 0.0001) and T1BR (p = 0.013) on dynamic contrast-enhanced magnetic resonance imaging (MRI). DWIG demonstrated a sensitivity of 94%, specificity of 38%, positive predictive value (PPV) of 76%, and negative predictive value (NPV) of 75% for meningiomas. This is the first pilot study in which DWIG fluorescence-guided surgery was used to visualize meningioma and dural tail intraoperatively with microscopy. DWIG is comparable with second-window ICG in terms of mean SBR. Gadolinium-enhanced T1 tumor signal may predict NIR fluorescence of the intracranial meningioma. Blood-brain barrier permeability as shown by K trans on dynamic contrast-enhanced MRI can contribute to gadolinium enhancement on MRI and to ICG retention and tumor fluorescence by NIR.

Update on the Impact of the University of Hawai'i Family Medicine Residency Program on the Family Physician Workforce in Hawai'i.

This study updates the previously-reported impact of the University of Hawai'i Family Medicine Residency Program (UHFMRP) on the state of Hawai'i family physician workforce. This study is a retrospective examination of all UHFMRP graduates from the program between 1996 and 2020. Graduate data regarding country or state of medical school, allopathic versus osteopathic training, current clinical practice, zip code of current clinical practice, current board certification, and current fellowship status were recorded between May and July 2020. Overall, 146 UHFMRP graduates completed the program between 1996 and 2020. Currently, 126 UHFMRP graduates have active medical licenses, with 121 graduates (96%, n=126) practicing in the United States, of whom 83 (69%, n=121) are practicing in Hawai'i. Of the 83 UHFMRP graduates practicing in Hawai'i, 67 graduates (81%, n=83) practice on O'ahu. UHFMRP graduates with active medical licenses in Hawai'i represent 23% (83 of 364) of the entire current family physician workforce in Hawai'i. The UHFMRP continues to make an impact on the Hawai'i State family physician workforce, and the retention rate of graduates in Hawai'i has remained relatively stable since 1996.

Fatal disseminated mucormycosis associated with COVID-19.

Secondary fungal infections are a critical problem that accompany immunosuppressive therapy for severe coronavirus disease 2019 (COVID-19). We report a fatal case of COVID-19 with disseminated mucormycosis diagnosed during autopsy. A 58-year-old man with diabetes was hospitalized for severe COVID-19 and treated with remdesivir, systemic steroids and tocilizumab. Following treatment, he was provided extracorporeal membrane oxygenation support. However, he died of multiple organ failure accompanied by pulmonary and kidney infarction, as revealed by computed tomography. Autopsy revealed that the infarction was caused by thromboangiitis due to mucormycosis in the brain, lungs, heart, liver and kidneys. Therefore, the diagnosis of disseminated mucormycosis was established. Disseminated mucormycosis is a rare complication of COVID-19. Although its early diagnosis is difficult, the disease progresses rapidly. Hence, we propose that immunosuppressive treatment for COVID-19 should be administered with caution considering the risk of developing severe opportunistic infections, such as mucormycosis.

A rare case of pancreatic neuroendocrine neoplasm causing Cushing's syndrome.

Pancreatic neuroendocrine neoplasms (PNENs) are relatively rare with a reported incidence of 1-2/100,000 and generally thought to originate from the precursor of the neuroendocrine cells including the islet and the pancreatic duct cells. About 65% of PNENs are non-functional. While insulinomas and gastrinomas are the most common functional PNENs, ACTH-producing PNENs are extremely rare. We herein present an extremely rare case of a patient with Cushing's syndrome caused by PNEN. A 46-year-old woman with edema in bilateral lower extremities and moon face was admitted with a suspicious pancreatic tumor. Enhanced computed tomography and endoscopic ultrasonography revealed a pancreatic tumor. The final diagnosis of ACTH-producing PNEN with Cushing's syndrome was based on clinical and biochemical test results and endocrinological studies. The symptoms associated Cushing's syndrome improved after pancreaticoduodenectomy for PNEN.

Balancing Performance and Human Autonomy With Implicit Guidance Agent.

The human-agent team, which is a problem in which humans and autonomous agents collaborate to achieve one task, is typical in human-AI collaboration. For effective collaboration, humans want to have an effective plan, but in realistic situations, they might have difficulty calculating the best plan due to cognitive limitations. In this case, guidance from an agent that has many computational resources may be useful. However, if an agent guides the human behavior explicitly, the human may feel that they have lost autonomy and are being controlled by the agent. We therefore investigated implicit guidance offered by means of an agent's behavior. With this type of guidance, the agent acts in a way that makes it easy for the human to find an effective plan for a collaborative task, and the human can then improve the plan. Since the human improves their plan voluntarily, he or she maintains autonomy. We modeled a collaborative agent with implicit guidance by integrating the Bayesian Theory of Mind into existing collaborative-planning algorithms and demonstrated through a behavioral experiment that implicit guidance is effective for enabling humans to maintain a balance between improving their plans and retaining autonomy.

Primary central nervous system lymphomas with massive intratumoral hemorrhage: Clinical, radiological, pathological, and molecular features of six cases.

Primary central nervous system lymphomas (PCNSLs) rarely exhibit intratumoral hemorrhage. The differential diagnosis of hemorrhagic neoplasms of the central nervous system (CNS) currently includes metastatic carcinomas, melanomas, choriocarcinomas, oligodendrogliomas, and glioblastomas. Here we present the clinical, radiological, pathological, and molecular genetic features of six cases of PCNSL associated with intratumoral hemorrhage. The median age of patients was 75 years, with male predominance. While conventional PCNSLs were associated with low cerebral blood volume (CBV), perfusion magnetic resonance imaging (MRI) revealed elevated CBV in three cases, consistent with vascular proliferation. All six cases were diagnosed pathologically as having diffuse large B-cell lymphoma (DLBCL) with a non-germinal center B-cell-like (non-GCB) phenotype; marked histiocytic infiltrates and abundant non-neoplastic T-cells were observed in most cases. Expression of vascular endothelial growth factor and CD105 in the lymphoma cells and the small vessels, respectively, suggested angiogenesis within the neoplasms. Neoplastic cells were immunohistochemically negative for programmed cell death ligand 1 (PD-L1), while immune cells in the microenvironment were positive for PD-L1. Mutations in the MYD88 gene (MYD88) (L265P) and the CD79B gene (CD79B) were detected in five and one case, respectively. As therapeutic modalities used for PCNSLs differ from those that target conventional hemorrhagic neoplasms, full tissue diagnoses of all hemorrhagic CNS tumors are clearly warranted.