A case of spermatic cord B-cell lymphoma relapsing to the brain in a dog.

A 13-year-old, intact male mixed-breed dog was referred to our clinic for lethargy and asthenia following an episode of gastroenteritis. As an incidental finding during abdominal ultrasound, a mass on the right spermatic cord was seen. Cytology of the mass revealed a monomorphic population of large, round cells with a lymphoid appearance. A bilateral orchiectomy was conducted, and histopathology revealed the presence of a B-cell lymphoma in the right spermatic cord. Based on clinical staging, which showed no involvement of other sites, no additional treatment was administered. Recheck evaluations were scheduled for every 3 mo thereafter. Five months after surgery, the dog developed left central vestibular syndrome with a paradoxical right-sided head tilt. An MRI of the brain showed multifocal lesions and, due to a rapidly worsening clinical condition, the dog was humanely euthanized. The histopathology of the brain lesions was consistent with B-cell lymphoma. Key clinical message: This is the first report of a primary spermatic cord lymphoma relapsing to the brain in a dog. Although rare, spermatic cord tumors should be included among the differential diagnoses for masses arising from the spermatic cord. If lymphoma is diagnosed, location to other sites, especially to the central nervous system, should be considered.

Un cas de lymphome à cellules B du cordon spermatique récidivant au cerveau chez un chien. Un chien de race mixte mâle intact de 13 ans a été référé à notre clinique pour léthargie et asthénie à la suite d'un épisode de gastro-entérite. Comme découverte fortuite lors d'une échographie abdominale, une masse sur le cordon spermatique droit a été observée. La cytologie de la masse a révélé une population monomorphe de grosses cellules rondes d'aspect lymphoïde. Une orchidectomie bilatérale a été réalisée et l'histopathologie a révélé la présence d'un lymphome à cellules B dans le cordon spermatique droit. Sur la base du stade clinique, qui n'a montré aucune implication d'autres sites, aucun traitement supplémentaire n'a été administré. Des évaluations de contrôle étaient programmées tous les 3 mois par la suite. Cinq mois après la chirurgie, le chien a développé un syndrome vestibulaire central gauche avec une inclinaison paradoxale de la tête du côté droit. Une IRM du cerveau a montré des lésions multifocales et, en raison d'une détérioration rapide de l'état clinique, le chien a été euthanasié sans cruauté. L'histopathologie des lésions cérébrales correspondait à un lymphome à cellules B.Message clinique clé :Il s'agit du premier rapport d'un lymphome primaire du cordon spermatique récidivant au cerveau chez un chien. Bien que rares, les tumeurs du cordon spermatique doivent être incluses dans les diagnostics différentiels des masses provenant du cordon spermatique. Si un lymphome est diagnostiqué, la localisation vers d'autres sites, en particulier vers le système nerveux central, doit être envisagée.(Traduit par Dr Serge Messier).

Allogeneic peripheral blood haematopoietic stem cell transplantation for the treatment of dogs with high-grade B-cell lymphoma.

Autologous peripheral blood haematopoietic stem cell transplantation (HCT) cures 33%-40% of dogs with high-grade B-cell lymphoma. We hypothesized, based on human allogeneic bone marrow transplantation literature, that transplanting dogs using canine donor leukocyte-matched CD34+ cells would lead to fewer relapses and increased cure rates. We retrospectively reviewed medical records of dogs diagnosed with high-grade B-cell lymphoma who received an identical allogeneic HCT. A total of 15 dogs transplanted at four facilities were identified. Five of fifteen dogs relapsed before transplant. The mean number of donor CD34+ cells/kg harvested and infused into recipient dogs was 8.0 × 106 /kg (range: 2.08 × 106 /kg-2.9 × 107 /kg). The median disease-free interval and overall survival of all dogs was 1095 days (range: 9-2920 days) and 1115 days (range: 9-2920 days), respectively. Two of five dogs, not in remission at transplant, died in the hospital. The median disease-free interval and overall survival of the remaining three dogs was 25 days (range: 15-250 days) and 1100 days (range: 66-1902 days), respectively. The median disease-free interval and overall survival of the 10 dogs who had not relapsed was 1235 days (range: 19-2920 days) and 1235 days (range: 19-2920 days), respectively. One dog died soon after discharge of presumed gastric-dilatation-volvulus. Eight of nine remaining dogs lived >4 yrs post-alloHCT, leading to a cure rate of 89%. Acute graft versus host disease was seen in three dogs. These results suggest that allogeneic HCT can cure ~50% more dogs than those treated with autologous HCT.

Primary Mediastinal Large B-Cell Lymphoma Achieved by Non-Cautery Assisted Transbronchial Mediastinal Cryobiopsy.

Transbronchial mediastinal cryobiopsy is a novel sampling strategy that shows improved diagnostic utility for mediastinal lesions, particularly in rare tumors and benign disorders, as compared to standard endobronchial ultrasound-guided transbronchial needle aspiration. During this procedure, electrocautery incision is frequently needed to advance the cryoprobe through the airway into the mediastinal lesion, which however results in increased operative difficulty and prolonged procedural time. Here we present a case of mediastinal large B-cell lymphoma successfully diagnosed by transbronchial mediastinal cryobiopsy without cautery-induced airway incision.

Endoscopic endonasal approach to the cavernous sinus Epstein-Barr virus-positive B cell non-Hodgkin lymphoma in a child: case report.

Cavernous sinus (CS) lymphoma without paranasal sinuses involvement is extremely rare in pediatric population and remains a diagnostic challenge due to its similarity to other tumors located in this area. An 8-year-old boy presented with a 6-day history of gradually developing ptosis in the right eyelid. After admission, his symptoms progressed within 24 h to include right-sided ophthalmoplegia consisting of oculomotor and abducens nerve palsies. Endoscopic endonasal approach (EEA) was performed urgently to decompress the CS and to obtain a diagnosis. The postoperative course was uneventful, and there was no complication related to the surgical approach. No immunodeficiency was identified. The histopathological diagnosis was an Epstein-Barr virus (EBV)-positive high-grade mature B cell non-Hodgkin lymphoma. He was initiated chemotherapy according to COG ANHL01P1 protocol. Two months after surgery, the third and sixth nerve palsies had resolved completely. Currently, he is well and has no clinical or radiological recurrence. This is the first pediatric case with EBV-positive CS lymphoma that underwent EEA for the diagnosis and decompression. In the pediatric population, EEA enables minimally invasive access to the CS and can play an alternative role in the management of CS lesions, either through biopsy or debulking.

DNA Methylation-Based Classification of Small B-Cell Lymphomas: A Proof-of-Principle Study.

Although most small B-cell lymphomas (SBCLs) can be diagnosed using routine methods, challenges exist. For example, marginal zone lymphomas (MZLs) can be difficult to rule-in, in large part because no widely-used, sensitive, and specific biomarker is available for the marginal zone cell of origin. In this study, it was hypothesized that DNA methylation array profiling can assist with the classification of SBCLs, including MZLs. Extramedullary SBCLs, including challenging cases, were reviewed internally for pathology consensus and profiled. By combining the resulting array data set with data sets from other groups, a set of 26 informative probes was selected and used to train machine learning models to classify 4 common SBCLs: chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, and MZL. Prediction probability cutoff was used to separate classifiable from unclassifiable cases, and show that the trained model was able to classify 95% of independent test cases (n = 264/279). The concordance between model predictions and pathology diagnoses was 99.6% (n = 262/263) among classifiable test cases. One validation reference test case was reclassified based on model prediction. The model was also used to predict the diagnoses of two challenging SBCLs. Although the differential examined and data on difficult cases are limited, these results support accurate methylation-based classification of SBCLs. Furthermore, high specificities of predictions suggest that methylation signatures can be used to rule-in MZLs.

Case Report: Spontaneous Remission of an Infraorbital Follicular B-Cell Lymphoma: Case Report and Review of the Literature.

Non-Hodgkin lymphomas comprise a heterogeneous group of malignancies, with a wide scope of clinical, radiological and histological presentations. In this paper, a case is presented of a 59-year-old white male with an infraorbital follicular B-cell lymphoma, which appeared as a painless mass in the left cheek. The lymphoma achieved spontaneous remission five and a half months after his diagnostic incision biopsy. The literature is reviewed, focusing on this rare site of presentation and spontaneous remission. In literature, only four cases have been reported with a follicular B-cell lymphoma of the cheek or infraorbital region, and only 26 cases of spontaneous remission of an extracranial non-Hodgkin lymphoma in the head and neck region have been described. To the authors' best knowledge, this is the first time spontaneous remission of an infraorbital follicular lymphoma could be observed. The nature of the processes inducing spontaneous remission remains obscure. It is important to recognize this phenomenon as this might prevent unnecessary treatment.

The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors.

Immune checkpoint blocking (ICB) is a promising new tool of cancer treatment. Yet, the underlying therapeutic mechanisms are not fully understood. Here we investigated the role of dendritic cells (DCs) for the therapeutic effect of ICB in a λ-MYC-transgenic mouse model of endogenously arising B-cell lymphoma. The growth of these tumors can be effectively delayed by antibodies against CTLA-4 and PD-1. Tumor-infiltrating DCs from mice having received therapy showed an upregulation of costimulatory molecules as well as an augmented IL-12/IL-10 ratio as compared to untreated controls. Both alterations seemed to be induced by interferon-γ (IFN-γ), which is upregulated in T cells and natural killer cells upon ICB. Furthermore, the enhanced IL-12/IL-10 ratio, which favors Th1-prone antitumor T-cell responses, was a consequence of direct interaction of ICB antibodies with DCs. Importantly, the capability of tumor-infiltrating DCs of stimulating peptide-specific or allogeneic T-cell responses in vitro was improved when DCs were derived from ICB-treated mice. The data indicate that ICB therapy is not only effective by directly activating T cells, but also by triggering a complex network, in which DCs play a pivotal role at the interface between innate and adaptive antitumor responses.

Resection of central nervous system lymphoma: a paradigm shift?

Central nervous system lymphomas (CNSL) are traditionally regarded as non-surgically treated tumors with a poor prognosis. Usually, only stereotactic biopsy is performed to establish the diagnosis, and most patients show disease progression within half a year. A recent study questioned this view, since patients who had surgical resection of CNSL manifestations prior to adjuvant therapy reportedly had a better outcome than patients who had biopsy only. We performed a retrospective analysis of our patient database to identify patients with CNSL who had undergone "accidental" tumor removal in our department between 2002 and 2013. Four patients had CNSL specific therapy following surgery. One patient received no further therapy because of his bad clinical status. Five patients with CNSL were treated surgically. Three patients were in complete remission at nine, thirteen and 45 months postoperatively, while two others had disease progression at 45 months, respectively. The median survival was 22.6 months. Gross total removal of CNSL may improve outcome. We present a series of five patients who had surgical resection of CNSL. While the importance of chemotherapy is beyond doubt, more data on the effect of surgery on the prognosis of patients with CNSL are needed. However, the paradigm of medical treatment only for CNSL is being challenged.

Tumoral Mimics of Subdural Hematomas: Case Report and Review of Diagnostic and Management Strategies in Primary B-Cell Lymphoma of the Subdural Space.

BACKGROUND: Subdural lymphomas are a rare subtype of primary central nervous system lymphomas that can radiographically mimic epidural blood and pose a diagnostic challenge. They can complicate treatment if not preemptively identified. METHODS: We present a case report of a subdural lymphoma that mimicked a compressive subdural hematoma, and we review the PubMed database for similar cases. RESULTS: A 77-year-old woman presented with a transient left facial droop and what appeared to be a subdural hematoma on computed tomography scan. The patient underwent surgery, during which grossly abnormal solid epicortical adherent tissue was noted instead of the expected appearance of a subdural hematoma. An intraoperative biopsy was suggestive of lymphoma, and the surgery was converted to a craniectomy. Pathology confirmed the diagnosis of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The patient underwent radiotherapy with no complications or recurrence. Magnetic resonance imaging demonstrated complete resolution of the mass at 3 months after treatment, at which time the patient underwent a synthetic cranioplasty. Seven case reports of primary dural lymphomas mimicking subdural blood were found, with variable pathologic subclassifications. CONCLUSIONS: Although rare, a primary dural lymphoma can be mistaken for a subdural hematoma on computed tomography scan. The most common subtype is low-grade extranodal marginal zone lymphomas. It is important to keep these diseases in the differential diagnosis, especially when there is incongruence between imaging and the clinical picture, as earlier detection correlates to a stronger therapeutic response.

An unusual case of pediatric-type follicular lymphoma: A case report.

RATIONALE: Pediatric-type follicular lymphoma (PTFL) is a rare neoplasm with features that differ from those of adult-type follicular lymphoma. Compared to patients with adult-type follicular lymphoma, PTFL patients often show an excellent response. Preoperative diagnosis is challenging and, therefore, an accurate diagnosis is based on the findings of postoperative pathological examination and immunohistochemistry. PATIENT CONCERNS: A 13-year-old boy presented with a slow-growing mass on the right side of his neck. DIAGNOSES: The patient was diagnosed with PTFL based on the findings of histopathological examination and immunohistochemistry. INTERVENTION: The mass was completely resected. OUTCOMES: After 12 months of postoperative follow-up, the patient achieved good recovery without recurrence. LESSONS: The optimal treatment for PTFL has not yet been defined. However, patients with PTFL always show satisfactory prognoses, regardless of treatment strategy (targeted radiotherapy, multiagent chemotherapy, or "watch and wait" strategy). Clinically, pathological and immunohistochemical analyses are necessary in the diagnoses of PTFL cases, especially for distinguishing PTFL from reactive follicular hyperplasia, to avoid unnecessary treatment.

Indolent In Situ B-Cell Neoplasms With MYC Rearrangements Show Somatic Mutations in MYC and TNFRSF14 by Next-generation Sequencing.

Systemic high-grade B-cell lymphomas (HGBCLs) with MYC gene rearrangements are clinically aggressive. In situ lesions with indolent behavior have not been described to date. We have identified 2 cases of in situ B-cell neoplasms with MYC rearrangements (IS-BCN, MYC) occurring, and focally confined to ≤4 lymphoid follicles in otherwise healthy individuals and without clinical progression despite minimal intervention (surgical only). Morphologically similar to systemic HGBCLs, the low power view of these lesions showed a starry sky pattern with numerous mitotic figures. High power imaging demonstrated these cells to be medium-large in size with irregular nuclear contours, immature chromatin, and prominent nucleoli. Immunophenotypically these cells were light chain restricted, positive for CD20, CD10, c-Myc, and dim or negative for BCL2 with a Ki67 proliferative index of >95%. By fluorescence in situ hybridization studies, we detected MYC translocations in these cells but no rearrangements in BCL2 or BCL6. Microdissection of neoplastic cells in these patients followed by targeted next-generation sequencing identified a mutation in MYC, D2N, and an indel in TNFRSF14. Mutations in ID3 or TCF3 were not identified. Although rare, these lesions should be separated from HGBCLs involving follicles but with systemic spread which has been previously described. Unlike systemic lymphomas with MYC gene rearrangements, these in situ B-cell neoplasms with MYC rearrangements did not require systemic therapy and no progression has been seen in either patient beyond 1 year (29 and 16 mo). Our work offers pathologic and biologic insight into the early process of B-cell neoplasia.

Ossified Chronic Subdural Hematoma and Subsequent Epstein-Barr Virus-Positive Large B-Cell Lymphoma: Case Report and Literature Review.

BACKGROUND: Ossified chronic subdural hematoma (CSH) associated with neoplasm has rarely been reported in the literature. We describe a patient with ossified CSH and underlying large B-cell lymphoma and discuss the relationship between lymphoma and CSH, emphasizing clinical characteristics, tumorigenic mechanism, and histopathologic analysis. CASE DESCRIPTION: A 46-year-old man with a history of alcohol abuse and a right frontotemporoparietal and left frontal ossified CSH that was diagnosed 2 years previously presented with headache and memory loss over 6 days. The patient was being followed with serial imaging, which showed the static state of the mass and no other lesions 7 months before admission. He underwent right frontotemporoparietal craniectomy to remove the ossified CSH and tumor. When the bone was lifted and the thin dura was opened, a hard, thick, ossified capsule was observed. No apparent tumor invasion was noted in the skull or epidural space. Despite refusing further chemotherapy and radiation therapy, the patient has been disease-free and working for 5 years. CONCLUSIONS: Based on reported cases and relevant literature, large B-cell lymphoma may be associated with ossified CSH.

Functional endoscopic sinus surgery in a cat with nasal tumor.

An 11-year-old, 5.8-kg, male European cat was presented with a 4-month history of sneezing, nasal discharge, respiratory distress and bilateral conjunctivitis. Physical examination showed bilateral hemorrhagic mucopurulent nasal discharge and stertorous respiratory sounds. An irregular shaped mass involving the aboral portion of the right nasal cavity and sphenoidal sinus was identified by computed tomography. The mass was localized endoscopically in the medium meatus and an endoscopic-guided biopsy was performed. B-cell lymphoma was diagnosed by histopathological and immunochemistry exams. Functional endoscopic sinus surgery allowed to completely remove the tumor and restore a normal nasal flow. The cat showed no recurrence of the neoplasia for 15 months after the functional endoscopic sinus surgery.

Multiple secondary cauda equina non-Hodgkin's lymphoma: a case report and literature review.

BACKGROUND: Secondary central nervous system involvement of non-Hodgkin's lymphoma (NHL) is rare and with poor prognosis, the most common pathological type is diffuse large B cell lymphoma (DLBCL). Although it can occur in any part of central nervous system, it rarely directly infiltrates the spinal cord or cauda equina. CASE PRESENTATION: We present the case of 64-year-old immunocompetent man with a worsening pain of waist and left lower extremity, accompanied by numbness and paresis of bilateral lower extremity for 20 days. His previous medical history included a resection of painless mass in the left groin in another hospital 7 months ago, and the pathological diagnosis was non-Hodgkin small B cell lymphoma. Gd-enhanced MRI and F-18 FDG PET-CT scan demonstrated multiple infiltrations in the cauda equina. During the operation, we removed as many as 11 subdural-extramedullary bean-size lesions involving multiple nerve roots. The paralysis of his left leg recovered rapidly after the operation. During the follow-up period of more than one year, he underwent standard R-CHOP chemical therapy, no evidence of recurrence was noted until the 13th month, the patient died because of intracranial relapse. CONCLUSIONS: Imaging examination is important in the diagnosis of multiple secondary cauda equina non-Hodgkin's lymphoma, and we highlight the significance of gadolinium-enhanced MRI and F-18 FDG-PET/CT in preoperative diagnosis as well as the previous history.

Pediatric Intracavernous Sinus Lesions: A Single Institutional Surgical Case Series and Review of the Literature.

BACKGROUND: Pediatric intracavernous sinus tumors are exceedingly rare and thus poorly characterized. Their neurosurgical management is challenging and diagnostic, and management guidelines are limited. OBJECTIVE: To report our institutional experience with the surgical resection of pediatric intracavernous sinus tumors. We also compare and contrast our results with the 14 cases of pediatric intracavernous sinus lesions in the current literature. METHODS: A retrospective descriptive analysis of consecutive pediatric patients (ages 0-18 yr) presenting to our institution with a diagnosis of an intracavernous sinus lesion was performed. From January 2012 to January 2017, 5 cases were identified. Eleven patients with secondary invasion of the cavernous sinus (2 meningiomas, 7 pituitary adenomas) or dermoid tumors involving the cavernous sinus (2) were not included in our review. RESULTS: Surgical resection via a frontotemporal orbitozygomatic approach was performed in all cases by a single senior neurosurgeon (M.L.). There were no perioperative or postoperative complications attributable to the surgery or approach. Four of 5 patients remained neurologically stable throughout the perioperative and postoperative period. The fifth patient had a complete resolution of their cranial neuropathies postoperatively. A pathological diagnosis that guided long-term management was obtained in all cases. CONCLUSION: Neurosurgical management of pediatric cavernous sinus lesions can be safely performed and critically guide future therapies. Surgeon familiarity with cavernous sinus and skull-base anatomy is critical to the successful management of these patients. The benefits of surgery should be balanced against the potential complications and need for a tissue diagnosis in children. The senior author had a significant experience with cavernous sinus approaches in adults prior to initiating use of the approach in the pediatric population.

Pediatric Diffuse Large B-Cell Lymphoma of the Frontal Sinus: A Case Report.

An 11-year-old male presented with right proptosis, bulbar conjunctivitis, and diplopia. Computerized tomography (CT) and magnetic resonance imaging revealed an enhancing mass involving the superio-medial orbit, ethmoids, frontal sinus, and anterior cranial fossa with skull base destruction. Diffuse large B-cell lymphoma was diagnosed via CT-guided biopsy. As a component of multidisciplinary care, the patient underwent frontal sinus cranialization, with orbital and skull base reconstruction. Trauma reconstructive principles guided recreation of orbital, frontal sinus, and anterior skull base anatomy. This rare primary location is undescribed in the pediatric literature.