Case # 3Slide Seminar

Los Angeles Society of Pathologists

March 13, 2007Randa Alsabeh, M.D.

Cedars-Sinai Medical Center

Clinical History

• 41 year old white male• Fevers, shaking chills, cough, shortness

of breath• Chest X-ray: innumerable bilateral

pulmonary nodules• Physical exam: right testicular mass

Differential Diagnosis

• Low grade lymphoma with transformation to large cell lymphoma

• NK/T-cell lymphoma

CD20

CD3

CD30

CD45

Bob-1

Oct-2

KAPPA

LAMBDA

Differential Diagnosis

• Low grade lymphoma with transformation to large cell lymphoma

• NK/T-cell lymphoma• T-cell rich large B-cell lymphoma with

areas of Diffuse large B-cell lymphoma!

X

X

EBER

EBER

EBV positive large B-cell lymphoma consistent with lymphomatoid granulomatosis, grade 2 and 3

Lymphoma of the Male Genital Tract

• Majority arise in the testes• Children: Acute leukemia (ALL)• Adults: Primary versus secondary spread

of systemic lymphoma• Prostate, epididymis and penis: reflect

widespread disease

Primary Testicular Lymphoma• 5% of all testicular malignancies• 7th to 8th decades, single most common primary

testicular neoplasm• Painless testicular enlargement, more bilateral

then germ cell tumors (50% of bilateral testicular neoplasms are lymphomas)

• Patients with B symptoms are younger, bilateral disease (Burkitt lymphoma)

• No association with previous trauma, inflammation, malformation or undescended testicle

Testicular Lymphoma

• Most common diffuse large B-cell lymphoma

• Low grade lymphomas, NK/T cell lymphoma, ALCL and angiotropic lymphoma

• 50% have systemic disease• Relapse occurs in CNS and contralateral

testicle

Lymphomatoid Granulomatosis (LYG)

• Angiocentric and angiodestructive lymphoproliferative disorder involving extranodal sites: lung (100%), brain (26%), kidney (32%), liver (29%) and skin (25-50%)

• Lymph nodes and spleen are rarely involved• Also known as angiocentric

immunoproliferative lesion (AIL)• Must be distinguished from extranodal NK/T-

cell lymphoma, nasal type

Lymphomatoid Granulomatosis (LYG)

• First description: unclear whether it a neoplastic or inflammatory process, 1972 by Liebow

• Initially misclassified as T-cell lymphoma• Clonal EBV sequences in B-cells

Lymphomatoid Granulomatosis (LYG)

• Adults, M/F: 2/1• Patients with immunodeficiency

disorders are at increased risk: HIV, allogeneic BMT, Wiskott-Aldrich syndrome, x-linked lymphoproliferative disorder

Lymphomatoid Granulomatosis (LYG)

• Mixed infiltrate of small lymphocytes, histiocytes, plasma cells, and variable numbers of large atypical lymphoid cells

• Angiocentric and angiodestructive infiltrates• EBV positive B-cells, CD30 positive in a

background of reactive T-cells-Grade I: EBV positive cells (

Morphology• D.D. includes benign angiocentric

lymphohistiocytic processes (mycobacterial or fungal infections,necrotizing sarcoidosis, and Wegener's granulomatosis)

• True granulomas are not usually present in lymphomatoid granulomatosis

Why is it important to make the diagnosis?

• A. Because hematopathologist love toclassify to justify their jobs

• B. Because it is clinically relevant• C. All of the above

“The urge to classify is a fundamental human instinct; like a predisposition to sin, it accompanies us into the world at birth and stays with us to the end”Hopwood A.T.Proceedings of the Linnean of London1957;171:230-234

Clinically Relevant

• Grade 1 and 2, uncertain malignant potential, waxing and waning, and may regress with interferon alfa-2b therapy and should be differentiated from T-cell rich B-cell lymphoma

• Grade 3 considered a variant large B-cell lymphoma, treated as aggressively but clinician should be alerted to the possibility of an underlying immune deficiency status

Prognosis and Management

• 27% complete remission without therapy• Majority with progressive disease with a

median survival of 14 months• CHOP 47% response with a mean

duration of 5.2 years• Interferon alfa-2b 67% response for

grade 1 and 2• Rituxan

• Our patient was treated with CHOP/Rituxan, underwent autologous stem cell transplantation and is in complete remission with complete resolution of his lung masses

Thank You