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Dr Stefan Dojcinov

University Hospital of Wales, Cardiff

Edinburgh Haematopathology Tutorial 2013 Cases 3 and 6

Case 3

Female, 83

Headaches and unsteadiness for 3 weeks. Found to have obstructive hydrocephalus due to a right cerebellar lesion.

Posterior fossa craniotomy and excision of right cerebellar lesion.

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CD20 CD3 PAX5

CD30 CD15 Oct2

EBER LMP1

Case 6

Male, 50 Shortness of breath, drenching night sweats and weight loss in November 2009. In early 2010 bilateral mid and lower zone lung masses, liver lesions and a (L) adrenal lesion thought to be non small cell lung cancer. Bronchial cytology not diagnostic. A bronchial biopsy showed necrosis with no malignancy. Treated empirically for NSCLC with gemcitabine and carboplatin, stopped in April 2010 but lung lesions soon after relapsed. Open biopsy left lower lobe lesion.

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CD20 CD20

CD3

CD30 CD15

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PAX5 Oct2

EBER LMP1

Cases 3 2003 – Classical Hodgkin Lymphoma (EBV+)

2010 - EBV+ Age Related Large B-cell Lymphoma (LyG – like features)

Cases 6

Lymphomatoid Granulomatosis – Grad 3

Lymphomatoid Granulomatosis

Extranodal EBV assciated B-cell LPD

Angiocentricity and angiodestruction

Immunological deficit

CD8 dysfunction

Association with ID (WA, HIV, HTLV1, Transplant)

Age 30s-40s M:F=2:1 Western population

Lung Skin Liver Kidney Brain No lymphadenopathy No bone marrow involvement

LyG – Epidemiology & Presentation

AWLP® LyG – Pathological features

Polymorphous angiocentric infiltrate

– Lymphocytes

– Plasma cells

– Variable immunoblasts and HRS-like cells depending on grade

Copious necrosis

NO GRANULOMAS

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CD20 AWLP ®

AWLP ®

CD20 PAX5 CD3

CD30 EBER CD15

LMP1

LyG - Grading

Grade 1 <5 EBER+ cells / HPF

No atypia

Grade 2 5-20 EBER+ cells / HPF

Occasional large cells

Small clusters

Grade 3 Numerous EBER+ large cells

No diffuse infiltrate

Case 3 Case 6

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Angioinvasion in EBV+ LP

Necrosis and angioinvasion in NK/T-cell and LyG

EBV capacity to induce monokines

Interferon-g–inducible protein-10 (IP-10)

Monokine induced by interferon-g (Mig)

Teruya-Feldstein et al. Blood, 1997; 90: 4099-4105

Age Related EBV+ LP (AREBVLP) or LyG

AREBVLP LyG

Presentation Nodal and extranodal Extranodal No diagnosis without lung involvement

Morphology Range of cell sizes Histiocytes, lymphocytes and PCs Angioinvasion Occasional granulmas Necrosis Numerous EBER+ cells (variable size)

Range of cell sizes Mainly lymphocytes Angioinvasion No granulomas Necrosis Numerous EBER+ cells (variable size)

Phenotype CD45+/- CD20 +/- PAX5+ OCT2+ BOB1+ CD30+ CD15+/- (68%) LMP1+

CD45+ CD20+ PAX5+ OCT2+ BOB1+ CD30+ CD15- LMP1-

Case 3 - Follow up

Extensive chest infection post op

Poor performance status

30G radiotherapy in April 2003

Died 3 months later with multiple spontaneous subdural haematomas and probable disease relapse

Case 6 - Follow up

Bone marrow negative, no lymphadenopathy

Received 8 courses of R-CHOP between November 2010 and June 2011

CT post 5 cycles showed a marked reduction in all lesions;

PET post 8 cycles showed no definite tumour

No further chemotherapy and remains in remission

Chest X-Ray is currently clear

LyG – Treatment and Prognosis

No standard protocols

Grades 1-2

Interferon alpha2b

Grade 3

Chemotherapy (R-CHOP)

Variable outcomes but median survival 14 months