, , 2011 HODGKIN LYMPHOMA

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1 European Federation of Cytology Societies 4tu Annual Tutorial in Cytopathology Trieste, June 6-10, 2011 HODGKIN LYMPHOMA

2 Classification The World Health Organization Classification of Lymphomas (2001) HODGKIN LYMPHOMA (HODGKIN DISEASE) (WHO 2001) Nodular N d l lymphocyte-predominant t Hodgkin lymphoma Classical Hodgkin lymphoma Nodular sclerosis classical Hodgkin lymphoma Mixed cellularity classical Hodgkin lymphoma Lymphocyte-rich y classical Hodgkin lymphoma Lymphocyte-depleted classical Hodgkin lymphoma

3 Power Doppler US pattern and FNC guide in Hodgkin lymphoma Lymph nodes may be partially involved from HL. Power Doppler may reveal an abnormal vascular pattern in a defined area of the lymph node that may be used as target in the FNC guide.

4 HODGKIN LYMPHOMA: diagnostic cells CD30 RS cells with lobated nuclei, clumped chromatin and large nucleoli, CD30+. Hodgkin cell in a polymorphus background with numerous eosinophils.

5 HODGKIN LYMPHOMA: diagnostic cells CD30 CD15 RS cells, CD15 and CD30 positives, with lobated nuclei, irregular chromatin and numerous large nucleoli.

6 HODGKIN LYMPHOMA: diagnostic cells CD30 RS mirror cells, CD30 positive, note the extremely large nucleoli.

7 HODGKIN LYMPHOMA: diagnostic cells CD15 CD30 Mononucleated HC cells with irregular chromatin and extremely large nucleoli. CD15 and CD30 positive, mononucleated HC cells.

8 HODGKIN LYMPHOMA: diagnostic cells A multinucleated cell with clumping chromatin A polyploid, l multinucleated, l t nucleolated l and hypercromasia. This cell may be RSH cells in a lymphoid background. considered a mummified RSH cells.

9 Nodular lymphocyte-predominant Hodgkin lymphoma NLHL: Cytological findings NLHL: diffuse lymphoid background with a variable number of large neoplastic monucleated cells known as lymphocytic and/or histiocytic Reed- Sternberg cell variants (L&H). The nuclei are often folded or multilobated, the chromatin is mostly vesicular, the nucleoli are usually multiple and smaller than those seen in classical HRS cells. Small lymphocytes, histiocytes and some polyclonal plasma cells are present in the background. ICC: L&H cells: CD15-, CD30-, CD20+, CD79a+, BCL6+ and CD45+. FC: not contributive, CD4/CD8 co-expression has been reported.

10 Nodular lymphocyte predominant, Hodgkin lymphoma CD20 Lymphocytic and/or histiocytic Reed-Sternberg cell variants (L&H). The nuclei may be round, folded or multilobated, the chromatin is mostly vesicular, the nucleoli are usually multiple and smaller than those seen in classical HRS cells. L&H cells are CD20+, CD15-,CD30-.

11 Classical Hodgkin lymphoma: Cytological findings Classical l Hodgkin lymphoma: HRS cells are large and show abundant, slightly basophilic, cytoplasm and two or more nuclear lobes or nuclei. Diagnostic RS cells have at least two nucleoli in two separate nuclear lobes. Mononuclear variants are termed Hodgkin cells, and the cells represent only a minority of the cellular infiltrate. The background is composed by reactive cellular infiltrate that varies according to the histological subtype. HRS cells are positive for CD30 in nearly all cases, for CD15 in the majority of cases and usually negative for CD45. Most HRS cells express the proliferation-associated nuclear antigen Ki-67. Classical Hodgkin lymphoma is classified as: Nodular sclerosis, Lymphocyte-rich, Mixed cellularity and Lymphocyte-depleted Nodular sclerosis contains a variable number of HRS cells in a background of small lymphocytes and other non-neoplastic inflammatory cells. Diagnostic cells may be rare or extremely numerous as in the syncitial variant. The HRS cells of this subtype tend to have more lobated nuclei with smaller lobes, and less prominent nucleoli. Lacunar HRS, determined by formalin fixation, which characterize this entity on histological sections are not observed on the smears. Eosinophils may be numerous. Mixed cellularity HRS cells are typical; the background cells consist of a mixture of eosinophils, neutrophils, histiocytes and plasma cells. One cell type may prevail over the others. The histiocytes may show pronounced epithelioid differentiation and may form granuloma-like like clusters. Lymphocyte-rich: scattered HRS cells in a background characterized by an abundance of small lymphocytes. Eosinophils and neutrophils may be present in small numbers. The small lymphocytes may be admixed with a large number of histiocytes with or without epithelioid features. Lymphocyte-depleted: rich in HRS cells and/or depleted in non-neoplastic neoplastic lymphocytes. In some cases pleomorphic HRS cells may predominate, producing a sarcomatous appearance. ICC: HC and HRS cells: CD15+, CD30+, CD20-, CD45-. DD: DLBCL: all types or metastasis in syncitial variant.

12 Classical Hodgkin lymphoma CD30 HL: One RSH cell (lower left) and two HC (center) in a lymphoid background. HL: A CD 30 positive, RSH cell.

13 Classical Hodgkin lymphoma CD15 HL: One RSH cell (lower left) and two HC (upper HL: one mirror cell and two, CD15 positive, HC. right) in an hematic and scantily lymphoid background.

14 Classical Hodgkin lymphoma HL: One HC with a large nucleolus in a lymphoid background. HL: RSH cells and numerous HC in a lymphoid background. Two eosinophils are present (lower left corner).

15 Classical Hodgkin lymphoma CD30 Extremely numerous and/or atypical RSH cell in a background of granulocytes. This picture may suggest a lymphocyte depletion. Extremely numerous CD30 positive RSH cell may suggest a lymphocyte depletion.

16 suppurative Hodgkin lymphoma RSH cells in a necrotic and acute inflammatory background

17 microscopic indirect signs Fibrosis fragments with intermingled lymphiod cells and nuclear crushes may be observed in HL smears. More than occasional or numerous eosinophils may suggest HL.

18 microscopic indirect signs An atypical and ill-preserved mononuclated cell in a back ground of granulocytes and an eosinophil. This image is suspect for HL. An atypical and ill- preserved multinucleated cell suspected for RSH cell. An sole atypical binucleated cell with large nucleoli suspected for RSH cell.

19 microscopic indirect signs An ill-preserved drs cell llin a necrotic and A granulomatous pattern without t a inflammatory background. This image is consistent clinical context might hide a HL. suspect for HL. At the same time granulomatous pattern may be observed in the follow-up of HL and NHL.