Case Presentation: 72 year old male presented with two months of fever, night sweats and malaise. He later developed dyspnea and was hospitalised twice. CT chest revealed scattered bilateral nodular lung opacities. He had dental work done prior to symptom onset and was thus thought to have right sided infective endocarditis (IE) with septic emboli. Workup included negative testing for culture negative IE, aspergillus, coccidioides, cryptococcus, histoplasma and HIV. Echo revealed no vegetations. PET scan showed bilateral pulmonary nodules and multiple cervical, mediastinal and hilar FDG avid lymph nodes. FNA of a lung nodule was negative for malignancy. Blood and urine cultures were negative. He was treated initially with Ceftriaxone and Doxycycline with resolution of fever and night sweats and decrease in size of the pulmonary nodules on repeat imaging. Antibiotics were discontinued after six weeks. Two weeks later he developed left cervical lymphadenopathy with recurrence of night sweats and weight loss. FNA of a cervical node was inconclusive. He underwent excisional biopsy but was readmitted before results were available due to worsening dyspnea. Repeat imaging revealed increased thoracic and abdominal lymphadenopathy along with splenomegaly and pleural effusions. Pathology from the excisional biopsy revealed atypical, medium to large sized lymphoid cells with prominent nucleoli and a background of small lymphocytes, eosinophils and histiocytes with the CD3 positive atypical lymphoid cells positive for MUM1, CD45 and EBER-ISH . He was diagnosed with stage 3B + lymphomatoid granulomatosis (LYG) given initial history of primary lung nodules and was started on R-DA-EPOCH, completing one cycle before being switched to R-CHOP.

Discussion: LYG is a rare B-cell lymphoproliferative disorder more common in males in the fourth to sixth decades of life (1-3). It universally presents with extra-nodal involvement (1). Though the lungs serve as the primary site of involvement, the CNS (38%), skin (17%), kidneys (15%) and liver (19%) may also harbor disease (3). This results in varied presentations and often leads to delayed diagnosis. Our patient’s clinical presentation was not unusual for LYG, as reported symptoms can range from fatigue, weight loss, fever and malaise to respiratory complaints, which are the most common (2). Patients may also be diagnosed incidentally on imaging (1). Other elements of this case however, are atypical. For example, the reduction in size and number of lung nodules, initially attributed to antibiotics was more likely a spontaneous event. Spontaneous regression of LYG lung nodules has been previously described, but the etiology has not been fully elucidated (2). The lymph node involvement in our patient ultimately led to the diagnosis, but this fact is itself unusual for LYG which is almost universally extra-nodal, with lymph node and bone marrow involvement considered rare (2). In one case series that included fifty-five patients, there were no cases of lymph node or bone marrow involvement (3). Treatment is dependent on the histologic grade at diagnosis. High grade LYG is treated with a regimen similar to that used to treat other aggressive lymphomas such as DA-EPOCH and R-CHOP.

Conclusions: Lymphomatoid granulomatosis is a rare disorder with a variable presentation often making the diagnosis difficult. It should however, be considered in the differential for patients with atypical febrile disorders, particularly when accompanied by lung nodules on imaging.

IMAGE 1: Image 1- PET scan prior to chemotherapy, with a lung nodule with moderately intense FDG activity highlighted