Burkittlike lymphoma probably diffuse blastoid Bcell lymphoma Harleen
Burkitt-like lymphoma (probably diffuse blastoid B-cell lymphoma) Harleen K. Sidhu MD 1 Jagmohan S. Sidhu MD 2 1. 2. Department of Dermatopathology, Clear. Path Diagnostics, Syracuse, NY, USA Department of Pathology and Laboratory Medicine, UHS Hospitals, Johnson City, NY, USA
Clinical Data • 74 -year-old Caucasian male presented in March 2013 with a 4 -month history of skin lesions on multiple sites of his body. • No fever, chills, night sweats, or weight loss. • Biopsy of a left flank skin lesion was performed.
H&E X 100 H&E X 400
CD 20 X 400 CD 10 X 400
BCL 2 BCL 6 MUM 1 Ki 67 X 400
Other Negative Stains • • • CD 2 CD 3 CD 4 CD 5 CD 7 CD 8
Diagnosis • Malignant lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (Burkitt-like lymphoma) • The possibility of this lymphoma being a diffuse blastoid B-cell lymphoma [probably a histologically aggressive variant of t(14; 18)negative diffuse follicular lymphoma] was raised after a jejunal mass, which was detected in this patient by PET/CT, was worked-up more extensively.
F 18 -FDG • Increased uptake in the multiple nodular areas of skin and subcutaneous tissue and in 3 small bowel sites • Range of maximum SUV in skin/subcutis: 10 -16. 8 • Range of maximum SUV in small bowel: 10. 5 -17. 2 • Maximum SUV (17. 2) in the small bowel is in jejunum and is associated with 1 cm of small bowel wall thickening. PET/CT Scan
Surgical Resection and Gross Description • About 5. 5 cm long segment of jejunum was resected to avoid possible perforation during chemotherapy. • A 5. 5 cm small bowel segment with attached mesenteric tissue was received fresh. A 5 cm x 2 cm “fish-flesh” like tumor was infiltrating the wall, protruding into the lumen and infiltrating the mesenteric tissue. Multiple small lymph nodes (0. 3 cm 1. 0 cm) were found in the mesentery. • Touch imprints of the jejunal mass were made and a piece of tumor was submitted for flow cytometric analysis. Rest of the specimen was fixed in 10% neutral buffered formalin.
Touch Imprint of Jejunal Mass Diff. Quik Stain X 1000
Scan of the Slides of Jejunal Mass CD 20 BCL 2 CD 10 BCL 6 MUM 1 CD 43 CD 57 HGAL LMO 2 c-MYC p 53 CD 21 CD 23 Td. T CD 2 CD 3 CD 4 CD 5 CD 7 CD 8 Ki 67 BCL 1 10 Recuts and 15 Unstained Sections of this block and 10 Recuts and 15 Unstained Sections of a skin block were submitted to the lymphoma workshop panel.
H&E Stain X 200 H&E Stain X 400
CD 20 X 400 CD 10 X 400
BCL 6 BCL 2 X 400 LMO 2 HGAL X 400
MUM 1 X 400 CD 57 X 400
CD 43 X 400 Ki 67 X 400 MYC X 400
Other Negative Stains • • • CD 2 CD 3 CD 4 CD 5 CD 7 CD 8 CD 21 CD 23 P 53 BCL 1 Td. T
Flow Cytometric Analysis of Jejunal Mass • CD 19+, CD 20+, CD 22+ (dim), CD 38+, CD 43+, CD 57+, surface kappa+, • CD 5 -, CD 10 -, CD 23 -, CD 79 b-, CD 200 -, FMC 7 -, CD 11 c-, CD 16 -, CD 56 -
FISH of Jejunal Mass Dual Fusion Probes Dual-Color Dual Fusion Probe Tri-Color Dual Fusion Probe Normal Ig. H-BCL 2 Ig. H: Green BCL 2: Orange Abnormal Ig. H-BCL 2 Ig. H: Green BCL 2: Orange Ig. H/MYC Translocation in 66. 50% nuclei Ig. H: Green MYC: Orange CEP 8: Aqua
FISH of Jejunal Mass BCL 6 Dual Color Break-apart Probe Normal BCL 6 3` BCL 6: Green 5` BCL 6: Orange BCL 6 Rearrangement (an overhanging 5` BCL 6 DNA sequence in 77% nuclei) 3` BCL 6: Green 5` BCL 6: Orange
FISH of Jejunal Mass Dual Color Probes No deletion/ monosomy of chromosome 7 chromosome 13 7 D 7 S 522, CEP 7 (7 q 31 - 7 p 11. 1 -q 11. 1) 7 p 11. 1 -q 11. 1 : Green 7 q 31 : Orange D 13 S 319, LAMP 1/13 q (13 q 14. 3 -13 q 34) 13 q 34 : Green 13 q 14. 3 : Orange
Cytogenetic Analysis of Jejunal Mass
CD 57 on the Previous Skin/Subcutis Specimen CD 57 X 400
HGAL and LMO 2 on Previous Skin/Subcutis Specimen HGAL X 400 LMO 2 X 400
Diagnosis • High grade B-cell lymphoma, Burkitt-like (most probably a diffuse blastoid B-cell Lymphoma) involving skin and small intestine
Differential Diagnosis of Aggressive Diffuse B-cell Lymphoma Morphologic Features Feature DBBCL DLBCL BL DLBC-LBL DBMCL B-LBL Growth Pattern Diffuse Diffuse Cell Size Medium Large Medium/ Large Medium Small/Medium Chromatin Fine Less fine Fine/Less fine Fine Prominent Nucleoli Absent Present Small/Medium/ Large Present/ Absent/ Present Mitotic Rate Very high High Very High/Very high “Starry-Sky” Present Absent/ Present/ Absent Present DBBCL: DBBCL Diffuse blastoid B-cell lymphoma DLBCL: DLBCL Diffuse large B-cell lymphoma BL: BL Burkitt lymphoma DLBCL-BL: DLBCL-BL Intermediate between DLBCL and BL DBMCL: DBMCL Diffuse blastoid mantle cell lymphoma B-LBL: B-LBL B-lymphoblastic lymphoma MORPHOLOGY Our case has features highlighted in the red. Morphologically our case is not a diffuse large B-cell lymphoma, but it can be any other entity in the differential.
Differential Diagnosis of Aggressive Diffuse B-cell Lymphoma Immunophenotypic Features Feature DBBCL DLBCL BL DLBCL-BL DBMCL B-LBL CD 10 + + or - - + or - BCL 2 + + or - - or + + or - + - BCL 6 + + or - - - MUM 1 + or - - - CD 57 + or - - - CD 43 + + or - - CD 5, CD 7, CD 8 + or - - - + or - - Td. T - - - + Cyclin D 1 - - + - Ki 67 LI Near 100% 40%-90% Near 100% IMMUNOPHENOTYPE Our case has features highlighted in the red. Immunophenotypically our case is not a DLBCL, DBMCL or B-LBL, but it can be DBBCL, BL or DLBCL-BL.
Differential Diagnosis of Aggressive Diffuse B-cell Lymphoma Cytogenetic Features Feature DBBCL DLBCL BL DLBCL-BL DBMCL B-LBL t(14; 18) - + or - - - c-MYC translocation - - or + + - or + - - c-MYC allelic loss + NK NK NK BCL 6 structural abnormalities + or - - - Extra copies of chromosome 18 + or - NK NK NK Monosomy 7 + or - - - + or - del (13)(q 14) + - - - NK: Not known CYTOGENETIC FEATURES Our case shows absence of t(14; 18), presence of MYC translocation and presence of BCL 6 rearrangement and, therefore, it is not a classic Burkitt lymphoma, can be called a Burkitt-like lymphoma or a Burkitt lymphoma with atypical features and is probably a diffuse blastoid B-cell lymphoma (DBBCL). Other entities in the differential diagnosis have already been excluded by morphology and immunophenotyping.
Why is Our Case Not a Classic Burkitt Lymphoma (BL)? • Our case has a CD 10+/BCL 2+/BCL 6+/MUM 1+/CD 57+ immunophenotype by immunohistochemistry • When a Burkitt lymphoma shows BCL 2 expression, it can be called Burkitt lymphoma only if it has Ig. H/MYC translocation without BCL 2 translocation and without BCL 6 translocation. • Our case shows BCL 6 rearrangement, Ig. H/MYC translocation and absence of BCL 2 translocation by FISH and conventional cytogenetic analysis.
Why did we raise the posssibility of a Diffuse blastoid B-cell lymphoma (DBBCL)? • Because it does not fit in any other entity in the differential diagnosis of aggressive B-cell lymphoma. • Because it shows many features of diffuse blastoid B-cell lymphoma that has been recently described and suggested as a histologically aggressive variant of t(14; 18)-negative diffuse follicular lymphoma*. * Chiu A et al. Mod Pathol 2009; 22: 1507 -1517
Treatment and Follow-Up • R-CHOP was initiated with almost 90% resolution of skin lesions after 1 cycle. • Chemotherapy was completed without any major complications. • Follow-up visit in December 2013: No lesions and no symptoms; normal PET/CT scan
Interesting Feature of Our Case Our case has a CD 20+/CD 10+/BCL 2+/BCL 6+/MUM 1+/CD 57+ immunophenotype with almost 100% Ki 67 labeling index, shows BCL 6 rearrangement and Ig. H/MYC translocation and shows absence of BCL 2 translocation by FISH and conventional cytogenetic analysis. These features are those of a Burkitt-like lymphoma (Burkitt Lymphoma with atypical features) and are suggestive of diffuse blastoid B-cell lymphoma that has been described and suggested as a histologically aggressive variant of t(14; 18)-negative diffuse follicular lymphoma in the literature (Chiu A et al. Mod Pathol 2009; 22: 1507 -1517).
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