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resulted in complete resolution of lymphadenopathy and systemic systems, after partial response to rituximab. The current case report, to our knowledge, describes the first case of successful treatment with siltuximab of plasmablastic microlymphoma arising in HHV8-associated MCD in an immunocompetent patient without significant side effects.

man disease (plasmablastic microlymphoma). Am. J. Surg. Pathol. 2006; 30; 123–127.

Secondary cutaneous involvement by systemic anaplastic lymphoma kinasenegative anaplastic large-cell lymphoma with 6p25.3 rearrangement DOI: 10.1111/his.12729

Author contributions G. Koenig and T. Stevens contributed to writing the manuscript. D. Peker collected and analysed the data, and wrote the manuscript.

Conflicts of interest The authors do not have any conflicts of interest to declare.

Ethics statement Ethics approval and/or informed consent were not required for this report, and no patient identification has been included in the manuscript. Gabriel Koenig Todd M Stevens Deniz Peker Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA 1. Frizzera G, Banks PM, Massarelli G, Rosai J. A systemic lymphoproliferative disorder with morphologic features of Castleman’s disease. Pathological findings in 15 patients. Am. J. Surg. Pathol. 1983; 7; 211–231. 2. Dupin N, Diss TL, Kellam P et al. HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8positive plasmablastic lymphoma. Blood 2000; 95; 1406–1412. 3. Courville EL, Sohani AR, Hasserjian RP, Zukerberg LR, Harris NL, Ferry JA. Diverse clinicopathologic features in human herpesvirus 8-associated lymphomas lead to diagnostic problems. Am. J. Clin. Pathol. 2014; 142; 816–829. 4. Peker D, Martinez AE, Schwartz MA, Cusnir M. Complete remission in 4 patients with human herpesvirus 8-associated multicentric Castleman disease using rituximab and liposomal doxorubicin, a novel chemotherapy combination. Clin. Adv. Hematol. Oncol. 2012; 10; 204–206. 5. van Rhee F, Wong RS, Munshi N et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014; 15; 966–974. 6. Li CF, Ye H, Liu H, Du MQ, Chuang SS. Fatal HHV-8-associated hemophagocytic syndrome in an HIV-negative immunocompetent patient with plasmablastic variant of multicentric Castle-

© 2015 John Wiley & Sons Ltd

Sir: We read with interest the recent report by Onaindia et al.1 describing three primary cutaneous anaplastic large-cell lymphomas (ALCLs) with 6p25.3 rearrangements and histological features similar to those that we have described in cases of lymphomatoid papulosis (LyP) bearing this rearrangement.2 Here, we extend these findings to include a case of secondary cutaneous involvement by systemic anaplastic lymphoma kinase (ALK)-negative ALCL with identical histological features, 6p25.3 rearrangement, and excellent long-term outcome. A 56-year-old male presented in 1982 with inguinal adenopathy. No skin lesions were present. Lymph node biopsy, on subsequent review, revealed ALKnegative ALCL extensively involving the node and showing a lymphohistiocytic histological pattern, as previously described.3 The patient recalled having adenopathy at other sites, although complete staging data were not available. The patient received cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy (number of cycles unknown), and achieved complete remission. He received maintenance chemotherapy including cyclophosphamide, chlorambucil, vincristine, and prednisone (doses/ schedules unknown). All chemotherapy was discontinued in 1995, and there were no known relapses between 1982 and 2011, when he presented with a solitary skin lesion on the right neck that showed involvement by ALK-negative ALCL. The patient was otherwise asymptomatic, and a staging positron emission tomography scan and bone marrow biopsy gave negative results. The patient received no further treatment following excision, and died without evidence of disease relapse in 2013 at the age of 87 years. The 2011 skin specimen showed an atypical lymphoid infiltrate involving the epidermis and dermis (Figure 1). The epidermotropic component contained Histopathology, 67, 923–935.

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small lymphocytes with convoluted, hyperchromatic nuclei, whereas the dermis contained sheets of large cells, including hallmark cells. The tumour cells were positive for CD2, CD3, CD4, CD30, and T-cell receptor (TCR)-bF1, with partial loss of CD5 and CD7, and negativity for TIA1, ALK, and TCR-cd, similarly to the original lymph node biopsy. Polymerase chain reaction studies showed clonal TCR-b and TCR-c rearrangements of the same size in both specimens, suggesting a clonal relationship (Figure 2). Fluorescence in-situ hybridization4 demonstrated 6p25.3 rearrangement in both specimens. We have reported 11 cases of a distinct subtype of LyP with unique histological features, including a biphasic morphological pattern, with large, transformed lymphocytes in the dermis, and pagetoid reticulosis-like infiltration of the epidermis of smaller atypical lymphocytes.2 Staining for CD30 was often biphasic, with strong staining in the dermis and weaker staining in the epidermis. All 11 cases with these features had 6p25.3 rearrangements (also known as DUSP22 rearrangements). The present case demonstrates that these features can be observed beyond the setting of primary cutaneous T-cell lymphoproliferative disorders, and provides further support for a relationship between the genetic and histological features as suggested by Onaindia et al.1 Cytokine-mediated homing might contribute to the pagetoid reticulosis-like epidermotropism in these cases. For example, we recently reported that ALCLs with 6p25.3 rearrangements overexpress the skin-homing chemokine receptor gene CCR8.5 The present case also emphasizes that the presence of a 6p25.3 rearrangement does not exclude the possibility of a systemic origin for ALCL involving the skin. Regardless of genetics, patients with ALCLs involving the skin require careful clinical evaluation and staging to ensure that they receive appropriate therapy. In a recent study on the genetics of systemic ALK-negative ALCL, we found 6p25.3 rearrangements in 30% of cases.6 These cases had favourable

Figure 1. Secondary cutaneous involvement by systemic anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma with 6p25.3 rearrangement. A, Low-power photomicrograph of skin lesion. B, Epidermotropic infiltrate of small lymphocytes. C, Sheet-like growth of large cells, including ‘hallmark’ cells (inset). D, Epidermotropic component staining for CD3. E, Dermal component staining for CD3. F, Epidermotropic component staining weakly for CD30. G, Dermal component staining strongly for CD30.

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Figure 2. Comparative molecular findings in the presenting lymph node (1982) and secondary cutaneous involvement (2011). A, Capillary electrophoresis tracings demonstrating clonal peaks for T-cell receptor-b from the lymph node. B, Tracings demonstrating identical peaks in the subsequent skin biopsy. C, Fluorescence in-situ hybridization (FISH) image from the lymph node biopsy obtained with a breakapart probe, showing one intact fusion signal (f) and one split signal (arrows), indicating a 6p25.3 rearrangement. D, FISH image from the subsequent skin biopsy, showing the same features.

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overall survival rates that were similar to those observed in systemic ALK-positive ALCL, as exemplified by the present case.

Acknowledgements This work was funded by Award Numbers R01 CA177734 (A. L. Feldman) and P50 CA97274 (University of Iowa/Mayo Clinic Lymphoma SPORE) from the National Cancer Institute.

Author contributions A. L. Feldman designed the study and wrote the manuscript. K. L. Grogg and D. J. Inwards contributed specimens and data. R. A. Knudson performed fluorescence in-situ hybridization studies.

Ethics Ethics review and informed consent were not required for this study.

Conflict of interest The authors declare no potential conflicts of interest.

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Andrew L Feldman Karen L Grogg Ryan A Knudson David J Inwards1 Department of Laboratory Medicine and Pathology, and 1 Division of Hematology, Mayo Clinic, Rochester, MN, USA 1. Onaindia A, Montes-Moreno S, Rodriguez-Pinilla SM et al. Primary cutaneous anaplastic large cell lymphomas with 6p25.3 rearrangement exhibit particular histological features. Histopathology 2015; 66; 846–855. 2. Karai LJ, Kadin ME, Hsi ED et al. Chromosomal rearrangements of 6p25.3 define a new subtype of lymphomatoid papulosis. Am. J. Surg. Pathol. 2013; 37; 1173–1181. 3. Pileri S, Falini B, Delsol G et al. Lymphohistiocytic T-cell lymphoma (anaplastic large cell lymphoma CD30+/Ki-1+ with a high content of reactive histiocytes). Histopathology 1990; 16; 383–391. 4. Feldman AL, Dogan A, Smith DI et al. Discovery of recurrent t (6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively-parallel genomic sequencing. Blood 2011; 117; 915–919. 5. Xing X, Flotte TJ, Law ME et al. Expression of the chemokine receptor gene, CCR8, is associated with DUSP22 rearrangements in anaplastic large cell lymphoma. Appl. Immunohistochem. Mol. Morphol. 2014; DOI: 10.1097/PAI.0000000000 000118. [Epub ahead of print]. 6. Parrilla Castellar ER, Jaffe ES, Said JW et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood 2014; 124; 1473–1480.

Secondary cutaneous involvement by systemic anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma with 6p25.3 rearrangement.

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