title: Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.
abstract: Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Magro
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Subramaniyam
authors.forename: Natasha
authors.initials: N
authors.lastname: Darras
authors.forename: Susan
authors.initials: S
authors.lastname: Mathew
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D015260:Neprilysin / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D015260:Neprilysin