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Slide Seminar
New and old challenges in the diagnosis of T-cell lymphomas

September 2nd, 17.00-19.00 Auditorium VI
Chairpersons: Daphne de Jong (Netherlands) and Laurence de Leval (Switzerland)
Case 1
Presented by: Ayoma Attygale, London, United Kingdom

The case was a second opinion and therefore the clinical history is scant.

A 76-year old male with generalised lymphadenopathy.

FNA – C2 (reactive).

Excision biopsy of a neck node.

No other clinical information available.
Slide 1Follicle centre and clear cellsClusters of clear cells in vicinity of HEVCD3CD4CD10PD1
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Case 2
Presented by: Philippe Gaulard, Créteil, France


Case history:

           A 60-year-old woman Caucasian presented with waxing and waning lymphadenopathies measuring up to3.5 cm. She had no B symptoms. A first lymph node biopsy was considered suspicious for a lymphoma but without definitive diagnosis. Persistent generalized lymphadenopathies resulted in a second lymph node biopsy in the occipital region. Staging with CT scan disclosed multiple adenopathies without hepatosplenomegaly. The bone marrow biopsy did not show tumor involvement. Biological tests were unremarkable: blood cell counts were normal without lymphocytosis, LDL level was normal and there was no hypergammaglobulinemia. Coombs test was negative

The lymph nodes spontaneously regressed and the patient was followed for 4 years without therapy. Two episodes of recurrent adenopathies occurred : relapses with similar pathological features in two lymph node biopsies were documented. Four years after initial diagnosis, she relapsed again with multiple adenopathies and B symptoms. A lymph node biopsy was performed and polychemotherapy was started.           

The images are from the second lymph node biopsy.

Fig 3d P Gaulard Case 2 PD1Fig 1 P Gaulard Case 2 H&E low magFig 2a P Gaulard Case 2 H&E Fig 2b P Gaulard Case 2 H&EFig 3a P Gaulard Case 2 CD3Fig 3b P Gaulard Case 2 CD7Fig 3c P Gaulard Case 2 CD10
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Case 3
Presented by: Daphne de Jong, Amsterdam, Netherlands

A 56 year old male presented with malaise, night sweats and 7 kilograms weight loss over the past few 2 months. He had noted an enlarged right tonsil. His previous medical history was only marked by aspecific cardial complaints 4 years earlier and by hypertension since 7 years for which he recieved medication. He did not use any other medication.

Physical examination and subsequent staging procedures including CT- and FDG-PET scanning showed cervical and upper abdominal lymphoadenopathy. All sites were PET positive. A diagnostic biopsy of the right tonsil was performed and chemotherapy treatment was started.
Slide 1ESP-SS-Hemat_case 3_HE2ESP-SS-Hemat_case 3_CD3ESP-SS-Hemat_case 3_CD20ESP-SS-Hemat_case 3_CD30ESP-SS-Hemat_case 3_HE1
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Case 4
Presented by: Wolfram Klapper, Kiel, Germany

13 year old girl. No clinical history of any skin disease. A maculopapular lesion at the right thight was resected and sent to histopathological examination.
Slide 1HE 400xPerforin 400xALK 400xCD3 400xCD30 400xHE 20x
HE 200x deepHE 200x
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Case 5
Presented by: Patty Jansen, Leiden, Netherlands

Male, now 60 years of age, presenting in 1989 with iliac and para-aortal lymphadenopathy which was diagnosed as stage II nodular sclerosis classical Hodgkin lymphoma, and for which combined chemo- and radiotherapy was given. In 1990, the patient developed patchy skin lesions on buttocks and back. The diagnosis mycosis fungoides (MF) was made on a skin biopsy, and therapy consisted of PUVA and topical corticosteroids with good results. In 2000, a tumorous skin lesion in the right axilla was interpreted as tumour stage MF with transformation and excision of the tumour was performed. In 2008, axillary and mediastinal lymphadenopathy were considered to be a recurrence of the same lymphoma diagnosed in 1989. In 2012, a large ulcerating tumour on the leg was consistent with transformed MF and treated with RT. At present, the patient is alive with some patches that respond well to corticosteroids.

Histology of the lymph nodes in 1989 and 2008 showed a similar picture of sclerosing bands and large, atypical Hodgkin-like cells in a background of lymphocytes, histiocytes, and eosinophils. Immunophenotypically, the blasts were positive for CD30 and CD15, but negative for PAX-5 and pan-T cell markers or cytotoxic granules.

Histology of the patches and tumor in the skin showed a picture consistent with (transformed) MF, with epidermotropic and blastic components. The blasts showed expression of CD30, CD2 (weak), and cytotoxic granules, but were negative for CD15.
Slide 1Slide 2
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Case 6
Presented by: Laurence de Leval, Lausanne, Switzerland

Male patient born in 1937 and originating from Mauritius island. No documented history of malabsorption or digestive symptoms. Presented in January 2009 with acute abdominal symptoms due to perforation of a duodenal ulcer. Underwent laparotomy and resection of a duodenal ulcerated lesion diagnosed as peripheral T-cell lymphoma (Mauritius Island, not available for review). Staging bone marrow was negative. Subsequently treated with 6 cycles of CHOP during the first semester of 2009. Was put on gluten-free diet, compliance uncertain. Readmitted in January 2010 for rectorragias and melena, digestive endoscopy disclosed a deep ulcer in the proximal jejunum as the source of bleeding. The patient underwent segmental intestinal resection (submitted specimen).

Details of biopsy: intestinal resection (19 cm) comprising the duodenum and proximal jejunum, performed in February 2010. Ulcerated tumor, 6 x 3 cm, located 1 cm from the proximal margin, no macroscopic evidence of villous atrophy in the surrounding mucosa. Fixation en buffered formalin.
Slide 1
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Case 7
Presented by: Falko Fend, Tübingen, Germany

31-year old female with moderate splenomegaly (18.5 cm, 240 grams), a history of chronic autoimmune thrombopenia and MGUS IgG lambda. The peripheral blood showed mild thrombopenia (128 G/L), normal leukocytes (6.1 G/L) with normal differential counts and normal Hemoglobin (139g/L). The bone marrow biopsy revealed a normocellular marrow for age with slight polyclonal plasmacytosis and two reactive appearing lymphoid infiltrates with mixed B- and T-cells with predominance of CD4+ cells and few cytotoxic cells. There was no evidence of infiltration by a hematological neoplasm. Autoimmune parameters were all negative. The FACS analysis of the peripheral blood showed normal T-cell subsets. There was no evidence of an increase in T-large granular lymphocytes (T-LGL). Since the patient clinically showed prominent B-symptoms, a splenectomy was performed to rule out lymphoma. Repeat FACS analysis of the PB some time after splenectomy showed an increase in CD4/CD8 DN T-cells (6,28%), mostly of alpha/beta-type. Increased soluble FasL (1564 pg/ml).

The submitted specimen shows the splenectomy. The increased lymphocytes in the red pulp predominantly expressed CD3, with a majority in addition showing CD5, CD7 and CD2.CD20+ B-cells were also increased, with normal architecture of B-cell areas. Within the red pulp, there is an expansion of CD4/CD8 DN T-cells. CD57 stains large numbers of T-cells both within the withe pulp T-cell areas, as well as the red pulp.CD56+ cells are mildly increased. There is an increase in TCRgamma positive T-cells in the red pulp, with a corresponding decrease of TCRalpha/beta+ (ßF1+) T-cells.

TIA1+ cells are increased significantly, granzyme B is expressed by a subpopulation. Molecular analysis of DNA extracted from the spleen specimen revealed a prominent clonal T-cell population using TCRbeta, TCRgamma and TCRdelta (BIOMED2) primer sets.
Slide 1Giemsa 1CD3 low powerCD4CD8TIA1 low powerCD20
betaF1Giemsa 3CD57betaF1 perifollicularTCRgamma red pulp
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Case 8
Presented by: Leticia Quintanilla-Fend, Tübingen, Germany

A previously healthy 15 year-old Mexican male began in August 2009 with upper respiratory symptoms, fever, fatigue, and general malaise. After 10 days without improvement a peripheral blood analysis was performed that showed Hb 9.6, Leukocytes 1200 with neutropenia (17%), platelets 138 000. The patient received treatment with antibiotics during 2 weeks (cephalosporins, 3th generation) without improvement. He was hospitalized with the diagnosis of fever of unknown origin. Physical examination revealed hepatosplenomegaly and cervical lymphadenopathy. At this time peripheral blood analysis showed pancytopenia and a bone marrow biopsy and aspirate were performed and interpreted as reactive with hemophagocytosis. A lymph node biopsy was taken (submitted). After 10 days of hospitalization the patient developed acute liver insufficiency with elevations of transaminases, jaundice and edema secondary to acute renal failure, in addition, he developed hypertrygliceridemia, hematuria, high blood pressure. The patient died after 30 days of hospitalization with multiple organ failure and disseminated intravascular coagulopathy, and 2 months after the beginning of his disease. All serology against HIV, Hepatitis virus A, B and C, EBV, Rubeola and Cytomegalovirus were negative.
Slide 1CD20.1.5xCD3.40xCD8.40xCD4.40xTIA.40xEBV. 20x
Double stains.EBER-CD8.40x
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