Diagnostic Slide Session Case DS-2010-03

Diagnostic Slide Session Case DS-2010-03

Miguel A. Guzman, MD1

Zissimos Mourelatos, MD2

1Neuropathology Fellow2Director, Neuropathology

Department of Pathology & Laboratory MedicinePENN Medicine

University of PennsylvaniaPhiladelphia

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

CD68 GFAP

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 lesionsIsolated fatal cases

•Rare associations: Following diffuse large B-cell lymphomaStroma-rich Castleman's diseaseLupus erythematosus

Br J Radiol. 2003 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 circumscribedAbundant karyorrhectic debris

•Scattered fibrin deposits

•Collections of large mononuclear cells

•Very scanty: plasma cells, neutrophils

•Plasmacytoid monocytes: often numerousif 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. 2010 Feb;134(2):289-

93.2. 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. 2003 Mar;36(1):65-8.

3. Shafqat S, Memon SB, Hyder S, Hasan SH, Smego RA Jr. Brainstem encephalitiswith Kikuchi-Fujimoto disease. J Coll Physicians Surg Pak. 2003 Nov;13(11):663-4.

THANK YOU!