Acute respiratory failure developing in a patient with lymphomatoid granulomatosis.

Lymphomatoid granulomatosis (LYG) is a rare B cell lymphoproliferative disorder associated with Epstein-Barr virus infection. LYG diagnosis is often difficult because of non-specific and varied radiological and pathological findings. The lung is the most common organ of LYG occurrence, but extrapulmonary lesions involving the central nervous system, skin, kidneys and liver are observed. A surgical biopsy is often inevitable for LYG diagnosis.We encountered a man in his 50s who presented with progressive dyspnoea. Extrapulmonary lesions were not observed. Although he developed respiratory failure within a short period, a low dose of corticosteroid relieved his symptoms. Video-assisted thoracoscopic lung biopsy revealed grade 1 LYG. The patient was successfully treated with chemotherapy, including rituximab. Only a few cases of LYG with progressive respiratory failure are reported, and most have been diagnosed via autopsy. Our case highlights the importance of performing a surgical lung biopsy at the appropriate time to diagnose LYG.

EBV Positive Lymphomatoid Granulomatosis Following Dental Extractions.

Epstein-Barr virus (EBV) associated lymphoproliferative disorders includes a diverse group of diagnoses, encompassing both B-cell and T-cell lineages. With EBV mucocutaneous ulcers becoming a World health Organization diagnosis in 2018, introduction of the disease entity will be beneficial to the practicing otolaryngologist. We are reporting a case of a 69-year-old male with history of rheumatoid arthritis on methotrexate, recently undergoing dental extractions, who then developed multiple oral ulcerations and bony erosions of his palate and alveolar ridge. Associated symptoms included a large 3.0 cm neck mass, splenomegaly, and pulmonary nodules. Histopathology showed EBV+ lymphomatoid granulomatosis. Upon removal of immunosuppressive agent, patient's symptoms improved with resolution of oral lesions, as well as systemic symptoms.

A Case of Lymphomatoid Granulomatosis in a Lymph Node with Unique Clinical and Histopathologic Features.

BACKGROUND Lymphomatoid granulomatosis (LyG) is a rare lymphoproliferative disorder associated with Epstein-Barr virus (EBV) in which there is an infection of B cells and numerous reactive T cells. The lymphoproliferative disorder progresses to organ infiltration and resultant dysfunction of affected organs. Histologically, it is characterized by a triad of polymorphic lymphoid infiltrate, angiitis, and granulomatosis. The lungs are the most commonly involved sites for lymphomatoid granulomatosis, but other sites that can be involved include the liver, skin, and central nervous system. The signs and symptoms of LyG can vary, and can produce generalized symptoms such as cough, shortness of breath, and chest tightness, but can vary depending on the location of LyG. CASE REPORT We report a case of a 60-year-old man who presented with altered mental status. Cross-sectional imaging of the brain was negative for any acute intracranial process, but a fine-needle biopsy of a retroperitoneal lymph node revealed nodular polymorphous mononuclear infiltrates containing atypical large EBV-positive B cells with positive EBER and CD30, consistent with lymphomatoid granulomatosis. The patient was started on a regimen of brentuximab/bendamustine, and instructed to follow up with Oncology on an outpatient basis. CONCLUSIONS Treatment options for lymphomatoid granulomatosis are based on the disease grading. Lymphomatoid granulomatosis can be classified by using a grading system determined by the number of EBV-positive large B cell malignant cells, along with necrosis. The most effective treatment for lymphomatoid granulomatosis is unknown, but at this time treatment protocols are based on the grade of the disease. The clinical and histological features of lymphomatoid granulomatosis are discussed in this case report.

A 67-Year-Old Woman With Abdominal Pain, Paresthesia, and Rapidly Expanding Lung Nodule.

CASE PRESENTATION: A 67-year-old woman with a medical history significant for hypertension, hyperlipidemia, type 2 diabetes mellitus, OSA, and schizophrenia was admitted multiple times the previous 3 months for generalized abdominal pain. Her most recent admission was unique for new onset bilateral upper and lower extremity weakness with paresthesia. Pertinent review of systems included malaise, fever, cough, left lower quadrant pain without weight loss, and rash. Previous evaluation included multiple CT scans of her abdomen that revealed colonic thickening. Ensuing colonoscopy revealed chronic ulcers with cytopathic changes consistent with cytomegalovirus.

Chronic lymphocytic infiltration with pontine perivascular enhancement responsive to steroids (CLIPPERS) and its association with Epstein-Barr Virus (EBV)-related lymphomatoid granulomatosis: a case report.

BACKGROUND: Chronic lymphocytic infiltration with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a neuro-inflammatory syndrome first described in 2010. It has a relationship with lymphoproliferative disorders that has not been fully elucidated. This case represents an unusual progression of CLIPPERS to Epstein-Barr Virus (EBV)-related lymphomatoid granulomatosis (LYG). The exact connection between CLIPPERS and LYG remains poorly understood. CASE PRESENTATION: We present a case of a 75-year-old man who was diagnosed with CLIPPERS with initial response to immunosuppression but later progressed to EBV-related LYG. EBV polymerase chain reaction (PCR) was detected in his cerebrospinal fluid (CSF), and repeat imaging revealed findings that were uncharacteristic for CLIPPERS; thereby prompting a brain biopsy which led to a diagnosis of EBV-related LYG. This case highlights the following learning points: 1) CLIPPERS cases are often part of a spectrum of lymphomatous disease, 2) CLIPPERS can be associated with EBV-related lymphoproliferative disorders such as LYG, and 3) EBV detection in CSF should prompt earlier consideration for brain biopsy in patients. CONCLUSIONS: Our case highlights the difficulty in distinguishing CLIPPERS from other steroid-responsive conditions such as neoplastic and granulomatous diseases. Given the association of CLIPPERS with EBV-related LYG as demonstrated in this case, we recommend testing for EBV in CSF for all patients with suspected CLIPPERS. An early referral for brain biopsy and treatment with rituximab should be considered for patients with suspected CLIPPERS who test positive for EBV in their CSF.

Neuroimages and Neuropathology of a Stroke-Like Cerebral Lymphomatoid Granulomatosis.

A 70-year-old man presented to the Emergency Department reporting the acute onset of non-fluent aphasia, hyposthenia, and hemi-anesthesia of the right body. Brain computerized tomography revealed a subcortical hypodense lesion in the middle cerebral artery territory. Neck ultrasounds of internal and external carotid arteries and of the vertebral arteries showed a focal moderate stenosis of the left internal carotid artery due to a soft atheromasic plaque. These findings that were initially consistent with a diagnosis of an ischemic stroke were not confirmed by magnetic resonance (MR). The latter showed an hyperintense lesion on FLAIR and T2-weighted sequences located in the left centrum semiovale, corona radiata, and thalamus, with a well-defined regular rim and a mild compressive effect on the lateral ventricle, with diffusivity restriction but without ADC reduction and with a punctate and serpiginous gadolinium enhancement on T1 sequences (Figure 1). Within the first day of observation, the patient started complaining progressive mental deterioration, in absence of any other possible causes, and a total body CT scan excluded any other organ involvement. Patient was then referred to the neurosurgeon in order to perform a brain biopsy. The neuropathology was compatible with the diagnosis of cerebral lymphomatoid granulomatosis (LG) (Figure 1).

Extranodal NK/T cell lymphoma and lymphomatoid granulomatosis in a patient with chronic lymphocytic leukaemia: Case report for a new perspective on Richter syndrome.

RATIONALE: Richter syndrome (RS) defines the transformation of chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma. Although the term RS is most often reserved for transformation of CLL into diffuse large B-cell lymphoma (DLBCL), and less frequently Hodgkin lymphoma , the list of cases with more variable presentations in the literature is growing. PATIENT CONCERNS: A 71-year-old Caucasian man initially consulted an otolaryngologist for a 1-year history of nasal congestion. DIAGNOSES: The asynchronous occurrence of 2 rare angiocentric Epstein-Barr virus (EBV)-related lymphoproliferative disorders in a patient with CLL, specifically clonally related lymphomatoid granulomatosis (LYG), and an extranodal NK/T-cell lymphoma, nasal type, are described herein. INTERVENTIONS: Radiation therapy and a regimen of cis-platinum were administered for the NK/T cell lymphoma, and ibrutinib for LYG. OUTCOMES: The patient remains in complete clinical remission 8 years after the diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and recurrent extranodal NK/T cell lymphoma, and 2 years after the diagnosis of clonally related LYG. LESSONS: Although the precise pathogenesis of RS remains incompletely understood, various molecular alterations, in particular long-term immunosuppression, may lead to RS, similar to the causal link existing between non-Hodgkin lymphomas and HIV infection, and post-transplantation lymphoproliferative disorders. EBV infection is linked to the pathogenesis of several types of lymphomas and found in a subset of patients with RS; immunosuppression, in the context of CLL or other pathological conditions or pharmacological agents, can disrupt the fine balance between virus and the host immune system, and result in EBV-driven lymphoproliferations of B-, T-, or NK-cell origin. The findings of our literature review thus suggest that such non-diffuse large B-cell lymphoma , non-Hodgkin lymphoma CLL transformations, may be considered as rare variants of RS.

A 53-Year-Old Man Presenting With Diplopia and Cavitary Lung Nodules.

CASE PRESENTATION: A 53-year-old Chinese man presented with 1 week of worsening diplopia and left-sided facial droop. His symptoms developed during a readmission for elective drainage and curettage of a perianal abscess that recurred despite drainage 2 weeks before. He denied having other neurologic symptoms, and did not report any cough, sputum production, night sweats, or fever. He was a lifelong nonsmoker with a history of polymyositis treated with mycophenolate mofetil for the last 4 years. He had undergone surgical resection for jejunal adenocarcinoma 12 years prior to this presentation. No evidence of recurrence was detected on surveillance gastrointestinal endoscopies and CT scans.

Cartilage hair hypoplasia with cutaneous lymphomatoid granulomatosis.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia characterized by short-stature, sparse hair and impaired cellular immunity. We describe a young girl who was diagnosed with CHH based on the findings of recurrent infections, short stature with metaphyseal chondrodysplasia, and a confirmed bi-allelic RMRP gene mutation. At 13 years, the patient developed an Epstein-Barr virus (EBV)-driven lymphoproliferative disorder involving the lung, which responded partially to chemotherapy. Simultaneously, she developed multiple indurated plaques involving her face, which had histological findings of granulomatous inflammation and EBV-associated low-grade lymphomatoid granulomatosis. The patient received a matched unrelated peripheral blood stem cell transplant at 15 years of age, and her immunological parameters and skin lesions improved. Lymphomatoid forms of granulomatosis and cutaneous EBV-associated malignancies have not been described previously in CHH. This case highlights the possibility of EBV-associated cutaneous malignancy in CHH.

Lymphomatoid Granulomatosis in a 14-Year-Old Boy with Trisomy 21 and History of B-Lymphoblastic Leukemia/Lymphoma.

BACKGROUND: Lymphomatoid granulomatosis is a EBV-driven lymphoproliferative disorder that has been reported in association with immunodeficiency, but only exceptionally in patients with hematopoietic malignancy. CASE REPORT: A 14-year-old boy with trisomy-21 and a history of B-lymphoblastic leukemia/lymphoma (B-ALL) diagnosed 1.5 years prior, on maintenance chemotherapy, presented with fever and respiratory symptoms. Chest X-ray revealed right-lower-lobe consolidation. He was treated for pneumonia but continued to be febrile with worsening respiratory status, with development of additional pulmonary and liver nodules. No infectious etiology was identified. Following nondiagnostic lung and liver biopsies, the largest pulmonary mass was resected. The histopathologic findings were diagnostic of lymphomatoid granulomatosis. There was no residual B-ALL. The patient's status continued to deteriorate and he died shortly thereafter. CONCLUSION: Relative immunosuppression due to maintenance therapy for B-ALL can lead to lymphomatoid granulomatosis.

Unsuspected lymphomatoid granulomatosis in a patient with antisynthetase syndrome.

Clinical diagnosis of lymphomatoid granulomatosis (LYG) often is difficult, especially in patients with multiple comorbidities. We present a 60-year-old woman with worsening fatigue, night sweats, unintentional weight loss, and dyspnea of 2 weeks' duration. Her medical history was remarkable for recent radiation therapy for recurrent breast cancer and antisynthetase syndrome complicated by interstitial lung disease and controlled with azathioprine. Computed tomography showed ground-glass opacities and nodular infiltrates in all lung lobes, raising concern for radiation pneumonitis and drug toxicity. Skin examination revealed erythematous and hemorrhagic papules, macules, and blisters on the lower leg. A diagnosis of LYG was made on a skin biopsy showing large angiocentric Epstein-Barr virus (EBV)-positive B cells. The patient soon progressed to develop nodal large B-cell lymphoma and died 6 weeks later. This rare report of LYG in a patient with antisynthetase syndrome highlights the diagnostic difficulty and aggressive course of LYG as well as the important role of skin biopsy in establishing the diagnosis.

Rare case of pulmonary lymphomatoid granulomatosis in conjunction with tuberculosis: A case report.

RATIONALE: Lymphomatoid granulomatosis is a very rare Epstein-Barr virus-driven lymphoproliferative disease. This disease has high mortality owing to its low incidence in conjunction with nonspecific presentations, which contribute to delays in diagnosis. PATIENT: An 87-year-old male had a week-long history of intermittent fever and general weakness. A chest radiograph showed multifocal patchy consolidations with nodular lesions. DIAGNOSES: Open lung biopsy using video-assisted thoracic surgery resulted in a diagnosis of grade III lymphomatoid granulomatosis. Three days after surgery, Mycobacterium tuberculosis complex was identified from the culture of sputum samples collected at admission. INTERVENTION AND OUTCOMES: Antituberculous treatment was commenced first. However, after 34 days of antituberculosis medication, the patient died owing to aggravated lymphomatoid granulomatosis. LESSONS: This case highlights the fact that rare diseases should also be considered in differential diagnosis, particularly with a common presentation such as multiple lung nodules. Furthermore, a diagnosis of pulmonary lymphomatoid granulomatosis was made after open lung biopsy. To our knowledge, this is the first case of lymphomatoid granulomatosis coexisting with active tuberculosis in the Republic of Korea, where tuberculosis is endemic.

The Complete Remission of Acquired Immunodeficiency Syndrome-associated Isolated Central Nervous System Lymphomatoid Granulomatosis: A Case Report and Review of the Literature.

A 49-year-old man presented with gradually progressive aphasia one month after being diagnosed with acquired immunodeficiency syndrome (AIDS). Brain magnetic resonance imaging showed multiple brain lesions with punctate and linear enhancement. A polymerase chain reaction detected Epstein-Barr virus (EBV) in the patient's cerebrospinal fluid. A diagnosis of isolated central nervous system lymphomatoid granulomatosis (CNS-LYG) was made based on the brain biopsy findings. The complete remission of CNS-LYG was achieved by anti-retroviral therapy (ART) alone. In the present case, the development of AIDS-associated CNS-LYG was considered to have been initiated by the reactivation of EBV in the CNS under immunosuppressive conditions. The patient's condition improved with the reconstitution of the patient's immune system.