Rare Presentation of Lymphomatoid Granulomatosis With CNS, Pulmonary, and Musculoskeletal System Involvement on 18F-FDG PET/CT.

Nivolumab in Lymphomatoid Granulomatosis (LYG) and Other Epstein-Barr Virus (EBV)-Positive Lymphoproliferative Disorders (LPDs) and Non-Hodgkin Lymphomas (NHLs) with Systemic and/or CNS Involvement: Preliminary Analysis of Efficacy and Safety from an Ongoing Phase II Study

Smoldering cutaneous course of lymphomatoid granulomatosis

A case of lymphomatoid granulomatosis presenting with cutaneous lesions

Phase 2 Study of Nivolumab in Epstein-Barr Virus (EBV)-Positive Lymphoproliferative Disorders and EBV-Positive Non-Hodgkin Lymphomas

AB0413 Systemic Therapy in Primary Sjögren Syndrome Patients

Patient: Male, 60-year-oldFinal Diagnosis: Lymphomatoid granulomatosisSymptoms: Altered mental statusMedication:—Clinical Procedure: —Specialty: OncologyObjective:Rare diseaseBackground: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.

Phase II Study of Interferon-Alpha and DA-EPOCH+/-R in Lymphomatoid Granulomatosis

Granulomatous Lymphoproliferative Disorders: Granulomatous Slack Skin and Lymphomatoid Granulomatosis.

Acute Cytomegalovirus Pneumonitis in Patient with Lymphomatoid Granulomatosis

A 72‐year‐old man presented with nausea, vomiting, cough, dyspnea, weight loss and an ulcerated nodule on the right calf of four month's duration. CT revealed multiple bilateral pulmonary nodules. Skin biopsy demonstrated an angiodestructive infiltrate with neutrophils, CD4+ T‐lymphocytes, CD20+ large, atypical lymphocytes and histiocytes in the reticular dermis and subcutis. The atypical lymphocytes were positive for EBV by ISH. PCR demonstrated a clonal immunoglobulin gene rearrangement. Lung biopsy showed histoplasmosis without evidence of a lymphoproliferative disorder or EBV infection. Further investigation revealed a low CD8 count, IgM deficiency and candidal esophagitis. Treatment consisted of itraconazole and rituximab. The cutaneous findings in this patient resemble lymphomatoid granulomatosis (LyG), an angiocentric and angiodestructive lymphoproliferative disorder involving extra‐nodal sites. While LyG can involve multiple organs, it primarily affects the lungs. The infiltrate consists of large, atypical EBV‐positive B‐cells admixed with reactive T‐cells. Although our patient's skin pathology resembles LyG, we favor the broader diagnosis of EBV‐associated diffuse large BCL since he had an isolated skin lesion without evidence of lung or other systemic involvement. We will compare the clinical and histologic findings in our patient to cases of LyG from our institution to help classify this entity among other cutaneous lymphoproliferative disorders.

Lymphomatoid granulomatosis (LYG) is a rare, T-cell-rich Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorder. Although LYG presents most often with lung involvement, up to half of affected individuals have concomitant cutaneous LYG. EBV-encoded RNA (EBER) is detected in the majority of pulmonary lesions but is often negative in skin lesions. Herein, we describe a case of concomitant EBV-positive pulmonary and EBV-negative cutaneous LYG in a 70-year-old woman. Histologically, both skin and lung biopsies demonstrated angiocentric necrosis with vascular wall compromise and a brisk inflammatory infiltrate comprised of plasma cells, histiocytes, and lymphocytes. Immunohistochemical studies on the skin biopsy demonstrated predominance of T cells and scattered B cells within the inflammatory infiltrate. Chromogenic in situ hybridization (CISH) for EBER was negative in the cutaneous infiltrate. The lung biopsy showed similar immunohistochemical findings but CISH for EBER demonstrated numerous EBV-positive B cells. Overall, this case demonstrates the variability of EBER positivity by CISH in multisystem LYG and underscores that its absence in cutaneous lesions does not exclude LYG from the differential diagnosis. Additionally, this case highlights the fact that cutaneous specimens should not be used in grading LYG by the World Health Organization criteria.

Lymphomatoid granulomatosis presenting as granulomatous orchitis

A 31-year-old patient in remission of acute lymphoblastic leukaemia (ALL), receiving oral maintenance chemotherapy (6-mercaptopurine, methotrexate (MTX), cyclophosphamide), developed a monoclonal, Epstein-Barr virus (EBV)-related lymphoproliferative disorder (LPD). Treatment consisted of excisional biopsy and the discontinuation of maintenance chemotherapy. To our knowledge, this is the first such report in an adult. The histological similarity to previous reports of 'lymphomatoid granulomatosis' following paediatric ALL suggests that they are the same disease. MTX may play a central role in the development of LPD in this setting. Although it is a rare complication of ALL, EBV-related LPD should be considered in patients who develop lymphadenopathy.

Lymphomatoid granulomatosis, a rare lymphoproliferative disorder, was previously defined by categorical pulmonary involvement with possible invasion into the skin, central nervous system, liver, and kidneys. However, recent reports have documented confirmed cases of lymphomatoid granulomatosis without lung involvement. Here, the authors describe a 70-year-old male with rheumatoid arthritis on methotrexate who presented with an ulcerating lesion on the right lower eyelid, initially suspicious for a basal cell carcinoma. Biopsy and immunohistochemical staining revealed grade 3 lymphomatoid granulomatosis. Further workup showed no systemic involvement. The patient's presentation was thought to be secondary to chronic immunosuppression with methotrexate. Upon withdrawal of the medication, the lesion regressed. To the authors' knowledge, this is the first case report of methotrexate-induced lymphomatoid granulomatosis presenting with a singular periocular cutaneous lesion.

We report a patient with pulmonary and cutaneous lymphomatoid granulomatosis with central nervous system (CNS) involvement manifesting as central diabetes insipidus and review other cases reported in the literature with attention to presence of endocrine manifestations and response to therapy. Imaging of the pituitary in our patient demonstrated a thickened hypophyseal stalk and empty sella appearance. CHOP chemotherapy proved to be an effective treatment for both the systemic and CNS involvement in our patient, but diabetes insipidus has persisted. We postulate that there was localized involvement of the stalk of the hypophysis by lymphomatoid granulomatosis, which led to a permanent lesion causing diabetes insipidus. We conclude that lymphomatoid granulomatosis may cause endocrine complications that may not resolve despite systemic remission, and while the optimal regimen for CNS involvement with lymphomatoid granulomatosis is unknown, certain patients can have long-term survival after treatment with systemic chemotherapy. Endocrine complications of malignant diseases often present diagnostic and therapeutic challenges to the internist and neuro-oncologist. Lymphoproliferative disorders such as lymphomatoid granulomatosis and malignant lymphomas may cause generalized illness, which may complicate the recognition of neurological and endocrine abnormalities. Once central nervous system (CNS) involvement is documented, there is controversy regarding which therapeutic approaches are indicated to treat the CNS lesions and the systemic disease. We present a patient with lymphomatoid granulomatosis involving the pituitary hypophysis and review the literature to search for a consensus on the best treatment of CNS involvement.