Diagnostic Slide Session Case DS Miguel A. Guzman, MD 1 Zissimos Mourelatos, MD 2 1 Neuropathology Fellow 2 Director, Neuropathology Department of Pathology & Laboratory Medicine PENN Medicine University of Pennsylvania Philadelphia

CLINICAL INFORMATION 44 yo woman with headache, poor balance and MRI that revealed a right occipital lobe tumor. Long standing history of intermittent lymphadenopathy: –1981 (15 yo): Fever and left axillary lymphadenopathy. Biopsy “reactive/benign adenopathy” –1991 (25 yo): Fever and cervical adenopathy: Biopsy: “reactive/benign” –2007 (41 yo): Fever, night sweats with hypermetabolic retroperitoneal and mesenteric enlarged lymph nodes, clinically suspicious for lymphoma: Biopsy: “focally necrotizing lymphadenopathy, negative for malignancy or infection”. The patient has history of allergies and multiple drug sensitivities with hypogammaglobulinemia detected in prior lab work up. Immunoglobulin levels now (performed on 1/19/09) show low IgA and IgM. MRI shows an enhancing, intra-axial, right occipital lobe mass with surrounding T2 prolongation.

DISCUSSION

CD3 CD20 CD68GFAP

CD68 (Macrophages) CD8 (Cytotoxic T cells)CD138 (Plasma cells)

KEY POINTS Histopathology: –Nodular, Necrotizing inflammatory lesion with macrophages, lymphocytes (predominantly T-cells). –Absence of acute inflammatory component –Negative stains and cultures for micro-organisms Clinical –Atypical MRI imaging mimicking tumor (differential included lymphoma or high grade glioma) –Long clinical history of previous diagnostic surgical procedure with negative histological findings for neoplasia in lymph nodes

Final Diagnosis Brain, right occipital, mass: Nodular, necrotizing, lymphohistiocytic inflammatory lesion consistent with CNS involvement by Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto Disease (KFD) (Necrotizing histiocytic lymphadenitis without granulocytic infiltration) CLINICAL FEATURES Uncommon, self-limited, systemic lymphadenitis of unknown etiology Localized lymphadenopathy, predominantly in the cervical region, accompanied by fever and leukopenia in up to 50% of the cases. Generally benign and self-limited Sometimes: Recurrent lymphadenopathy Accompanying skin lesions Isolated fatal cases Rare associations: Following diffuse large B-cell lymphoma Stroma-rich Castleman's disease Lupus erythematosus Br J Radiol Sep;76(909):656-8.

Source: Rosai: Surgical Pathology 9th edition Kikuchi-Fujimoto Disease (KFD) Pathogenesis Necrosis due to cytoxic lymphocyte-mediated apoptotic cell death Etiology unknown Early suggestion that Toxoplasma may be involved not substantiated Epstein–Barr virus (EBV), human herpesvirus (HHV)- 6, HHV-8, and other viruses implicated: evidence not conclusive

Source: Rosai: Surgical Pathology 9th edition Kikuchi-Fujimoto Disease (KFD) Histopathology Paracortical necrotizing lesions Focal Well circumscribed Abundant karyorrhectic debris Scattered fibrin deposits Collections of large mononuclear cells Very scanty: plasma cells, neutrophils Plasmacytoid monocytes: often numerous if diffuse growth may simulate malignant lymphoma. Occasionally: prominent secondary xanthomatous reaction Electron microscopy: tubuloreticular structures and intracytoplasmic rodlets: similar to those in lupus erythematosus Our case

Differential: Lymphoma (Hodgkin’s and non-Hodgkin’s) Infections including: -EBV/CMV -HIV -Cat Scratch Disease -Tuberculous adenitis -Autoimmune – in particular SLE is an important consideration as many patients initially diagnosed with Kikuchi’s dz have subsequently developed SLE (tubuloreticular structures in the lymphocytes and endothelial cells in SLE have been observed similar to those seen in Kikuchi’s dz) Kikuchi-Fujimoto Disease (KFD)

Pre-operative MRI T1 post-gadolinium (1/19/2009) Follow up MRI T1 post- gadolinium (2/11/2010) FOLLOW UP AFTER ONE YEAR

Pre-operative MRI T1 post-gadolinium (1/19/2009) Follow up MRI T1 post- gadolinium (2/11/2010) FOLLOW UP AFTER ONE YEAR

Comments Involvement of Central Nervous System occasionally occurs in KFD typically in the form of aseptic meningitis Brain parenchymal involvement by KFD is exceptionally rare, documented only by radiographic studies In rare cases, KFD is associated with common variable immunodeficiency (of note is that this patient has hypogammaglobulinemia). References: 1.Hutchinson CB, Wang E. Kikuchi-Fujimoto disease. Arch Pathol Lab Med Feb;134(2): Chien YH, Yang YH, Hwu WL, Chou CC, Chiang BL. Common variable immunodeficiency with hypoglycemia, Kikuchi lymphadenitis, and hemiparesis in two siblings. J Microbiol Immunol Infect Mar;36(1): Shafqat S, Memon SB, Hyder S, Hasan SH, Smego RA Jr. Brainstem encephalitiswith Kikuchi-Fujimoto disease. J Coll Physicians Surg Pak Nov;13(11):663-4.

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