—  SPECIALTY CONFERENCE HANDOUT  —

Hematopathology
Thursday, March 29, 2007, 7:30 PM
Convention Center 5 A/B

Hodgkin Lymphoma and Its Differential Diagnosis

Moderator:

MARSHA C. KINNEY
University of Texas Health Science Center
San Antonio, TX


Disclosure: The speakers have indicated they have nothing to disclose.




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Case 1 - Click here for Text and References

Submitted by: Yashoda Natkunam - Stanford University Medical Center, Stanford, CA

Clinical Summary:

The patient is a 61-year old man who presents with a mesenteric mass. A 5.0 cm mesenteric lymph node was excised. Approximately thirty years previously the patient had undergone a supraclavicular lymph node biopsy and the diagnosis of nodular sclerosis classical Hodgkin lymphoma was rendered for which he received chemotherapy and radiation. The patient had undergone two subsequent lymph node biopsies at 4 and 13 years after his initial treatment. Both of these biopsies had shown reactive follicular hyperplasia with progressive transformation of germinal centers.


Case 1 - Slide 1
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Case 1 - Figure 1 - Low magnification image showing that the lymph node architecture is effaced by a nodular lymphoid proliferation studded with scattered atypical large cells.

Case 1 - Figure 2 - Diffuse lymphoid infiltrate associated with sclerosis.

Case 1 - Figure 3 - Nodular and diffuse architecture with residual germinal centers.

Case 1 - Figure 4 - Scattered atypical large cells in a lymphocyte-rich background.

Case 1 - Figure 5 - High magnification image showing atypical large cells in a lymphocyte-rich background.

Case 1 - Figure 6 - CD20 - An immunostain for CD20 highlights B cell-rich nodules within which are atypical large CD20-positive cells.

Case 1 - Figure 7 - CD20 - An immunostain for CD20 highlights atypical large cells within and outside lymphoid nodules.

Case 1 - Figure 8 - CD21 - An immunostain for CD21 highlights dendritic meshworks imparting a nodular architecture.




Case 2 - Click here for Text and References

Submitted by: Judith Ferry - Massachusetts General Hospital, Boston, MA

Clinical Summary:

The patient was a 33-year-old attorney who presented initially with mild dyspnea, possibly in association with a cold. His symptoms resolved, but a few weeks later he noted an unusual sensation, described as a tightening or tingling, in his right chest on deep inspiration. He also had low-grade fever but no weight loss or convincing night sweats. He had a history of infectious mononucleosis during high school, but his past medical history was otherwise unremarkable.

Radiographic evaluation revealed a 6 x 8 cm mediastinal mass. Biopsies of the mass were performed.


Case 2 - Slide 1
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Case 2 - Figure 1 - There is a dense, diffuse infiltrate of atypical lymphoid cells, with a mottled light and dark pattern at low power.

Case 2 - Figure 2 - There is a dense, diffuse infiltrate of atypical lymphoid cells, with a mottled light and dark pattern at low power.

Case 2 - Figure 3 - The infiltrate is associated with sclerosis.

Case 2 - Figure 4 - In some areas there are scattered cells resembling lacunar cells scattered in a background of reactive cells.

Case 2 - Figure 5 - A few eosinophils are present.

Case 2 - Figure 6 - High power shows large atypical cells, including cells resembling lacunar cells and one binucleated Reed-Sternberg-like cell, with admixed small lymphocytes.

Case 2 - Figure 7 - Low power in this area shows a more uniform infiltrate of atypical cells.

Case 2 - Figure 8 - In these images, most atypical cells have large, round to oval nuclei, vesicular chromatin, prominent nucleoli and moderately abundant pale cytoplasm, and there are fewer admixed reactive cells than in figures 4 and 6.

Case 2 - Figure 9 - In these images, most atypical cells have large, round to oval nuclei, vesicular chromatin, prominent nucleoli and moderately abundant pale cytoplasm, and there are fewer admixed reactive cells than in figures 4 and 6.




Case 3 - Click here for Text and References

Submitted by: Stefania Pittaluga - National Cancer Institute, Washington, DC

Clinical Summary:

83 year old male who presented with generalized adenopathy, night sweats, and fatigue; he was treated with hyper-CVAD and went into CR for four months. Recurrent adenopathy developed in the right neck.

Submitted biopsy: Lymph node, right inguinal (pre-treatment)

Flow cytometry: 16% aberrant T cells with down-regulation of CD3 and CD7.

Other markers: CD2 moderately positive; CD5 moderately positive, CD8 negative, CD13/33 negative, CD19 negative, CD20 negative, CD22 negative, CD23 negative, CD38 variably positive, CD56 negative, kappa negative, lambda negative.

Molecular studies were performed. Southern blot analysis using EcoRI, BamH1+HindIII, XbaI using TCRbeta (constant region and J2) showed rearranged bands in all three digestions.

TCRgamma PCR: Clonal rearrangement detected

IgH PCR: Polyclonal pattern detected.


Case 3 - Slide 1
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Case 3 - Figure 1 - Effaced nodal architecture with scattered Reed-Sternberg-like cells in an inflammatory background, H&E.

Case 3 - Figure 2 - Cytological features of the RS-like cells are best appreciated at higher magnification, H&E.

Case 3 - Figure 3 - Mild cytologic atypia of background lymphocytes is noted with admixed eosinophils and plasma cells.

Case 3 - Figure 4 - CD3 - The RS-like cells and background lymphocytes are both positive for CD3; the cytologic atypia of background lymphocytes is best appreciated with the CD3 immunostain.

Case 3 - Figure 5 - CD3 - The RS-like cells and background lymphocytes are both positive for CD3; the cytologic atypia of background lymphocytes is best appreciated with the CD3 immunostain.

Case 3 - Figure 6 - CD15 - The RS-like cells are positive for CD15 (membranous and golgi), while background lymphocytes show a golgi pattern of staining.

Case 3 - Figure 7 - CD30 - The RS-like cells are positive for CD30; background lymphocytes are largely negative.

Case 3 - Figure 8 - Pax-5 - The RS-like cells show weak positivity for PAX-5.

Case 3 - Figure 9 - CD10 - A subset of background lymphoid cells stain positively for CD10.

Case 3 - Figure 10 - CD21 - CD21 stains dendritic meshworks, which are not only related to residual B-cell areas, but are also associated with high endothelial venules.




Case 4 - Click here for Text and References

Submitted by: Jonathan Said - UCLA Center for Health Sciences, Los Angeles, CA

Clinical Summary:

The patient is a 76-year old man with a history of left supraclavicular and cervical lymphadenopathy for at least one year without splenomegaly or constitutional 'B' symptoms. On specific questioning he was found to have a history of rheumatoid arthritis, but was never on immunosuppressive medication. The lymph node biopsy was from the supraclavicular lymph node.

(I am grateful to Dr. Timothy S. Braverman at the Jewish Hospital in Cincinnati OH for permission to use this case.)


Case 4 - Slide 1
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Case 4 - Figure 1 - H&E original X100 - Low power photomicrograph reveals a reactive germinal center and expansion of the parafollicular region by a mixture of small lymphocytes and histiocytes giving a 'mottled' appearance.

Case 4 - Figure 2 - H&E original X100 - There is a focus of necrosis with acute inflammation.

Case 4 - Figure 3 - H&E original X100 - Mixed lymphocytic and histiocytic proliferation and scattered large cells with prominent nucleoli resembling Hodgkin cells.

Case 4 - Figure 4 - H&E original X200 - Reed Sternberg like cells with prominent nucleoli and perinucleolar clearing in a background of small lymphocytes and scattered large mononuclear cells.

Case 4 - Figure 5 - H&E original X200 - A Reed Sternberg like cell (top panel) and apoptotic mummified cell (bottom) with a mixed background which includes eosinophils.

Case 4 - Figure 6 - H&E original X200 - A Reed Sternberg like cell (top panel) and apoptotic mummified cell (bottom) with a mixed background which includes eosinophils.

Case 4 - Figure 7 - H&E original X240 - Large mononuclear cells with prominent nucleoli and amphophilic cytoplasm in a mixed background.

Case 4 - Figure 8 - H&E original X240 - Large multilobed Reed Sternberg cell with a wreath like configuration in a mixed background including mononuclear cells, lymphocytes, histiocytes, and eosinophils.

Case 4 - Figure 9 - LCA - H&E original X100 - Immunostains reveal that the large cells are positive for CD45 (LCA) and CD20, but negative for CD15.

Case 4 - Figure 10 - CD20 - H&E original X100 - Immunostains reveal that the large cells are positive for CD45 (LCA) and CD20, but negative for CD15.

Case 4 - Figure 11 - CD20 - H&E original X100 - Immunostains reveal that the large cells are positive for CD45 (LCA) and CD20, but negative for CD15.

Case 4 - Figure 12 - CD15 - H&E original X100 - Immunostains reveal that the large cells are positive for CD45 (LCA) and CD20, but negative for CD15.

Case 4 - Figure 13 - Oct 2 - H&E original X100 - Large cells are positive for both Oct2 and Bob.1

Case 4 - Figure 14 - Bob.1 - H&E original X100 - Large cells are positive for both Oct2 and Bob.1

Case 4 - Figure 15 - CD30 - H&E original X140 - Immunoblasts in the region of the germinal centers and scattered large cells are positive for CD30.

Case 4 - Figure 16 - CD30 - H&E original X140 - Immunoblasts in the region of the germinal centers and scattered large cells are positive for CD30.

Case 4 - Figure 17 - EBV EBER - H&E original X100 - Many of the large cells are positive for EBV EBER by in-situ hybridization.