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HHV8-Positive Castleman Disease and in Situ Mantle Cell Neoplasia Within Dermatopathic Lymphadenitis, in Longstanding Psoriasis

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HHV8-Positive Castleman Disease and in Situ Mantle Cell Neoplasia Within Dermatopathic Lymphadenitis, in Longstanding Psoriasis diagnostics Interesting Images HHV8-Positive Castleman Disease and In Situ Mantle Cell Neoplasia within Dermatopathic Lymphadenitis, in Longstanding Psoriasis Magda Zanelli 1,* , Luca Stingeni 2 , Maurizio Zizzo 3,4, Giovanni Martino 5, Francesca Sanguedolce 6, Andrea Marra 7, Barbara Crescenzi 8, Stefano A. Pileri 9 and Stefano Ascani 5 1 Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42112 Reggio Emilia, Italy 2 Dermatology Section, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy; [email protected] 3 Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; [email protected] 4 Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy 5 Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy; [email protected] (G.M.); [email protected] (S.A.) 6 Pathology Unit, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy; [email protected] 7 Centre of Hemato-Oncology Research (CREO), Institute of Hematology, University and Hospital of Perugia, 06129 Perugia, Italy; [email protected] 8 Laboratory of Molecular Medicine, CREO, Azienda Ospedaliera di Perugia, University of Perugia, 06129 Perugia, Italy; [email protected] Citation: Zanelli, M.; Stingeni, L.; 9 Haematopathology Division, European Institute of Oncology—IEO IRCCS, 20141 Milan, Italy; Zizzo, M.; Martino, G.; Sanguedolce, [email protected] F.; Marra, A.; Crescenzi, B.; Pileri, * Correspondence: [email protected]; Tel.: +39-0522-296372; Fax: +39-0522-296945 S.A.; Ascani, S. HHV8-Positive Castleman Disease and In Situ Mantle Abstract: A 73-year-old man presented with multiple lymphadenopathy. He had a 20-year history Cell Neoplasia within Dermatopathic of palmoplantar psoriasis evolved to a diffuse erythrodermic picture in the last two years. Topic Lymphadenitis, in Longstanding and systemic medications including prednisolone, acitretin, anti-IL17 (ixekizumab), TNF inhibitor Psoriasis. Diagnostics 2021, 11, 1150. (adalimumab), anti-IL23 (guselkumab), methotrexate, cyclosporine, and phosphodiesterase 4 in- https://doi.org/10.3390/ diagnostics11071150 hibitor (apremilast) were ineffective. Repeated skin biopsies excluded mycosis fungoides, confirming psoriasis; molecular analysis of T-cell receptor genes ruled out clonality. The axillary lymph node Academic Editor: Chyi-Chia histology documented a dermatopathic lymphadenitis, often associated with chronic cutaneous Richard Lee inflammatory diseases. At an accurate morphological evaluation, features of HHV8-positive multi- centric Castleman disease were observed. Moreover, in a few follicles, in situ mantle cell neoplasia Received: 31 May 2021 was identified. The translocation t(11;14)(q13;q32), characteristic of mantle cell lymphoma, and the Accepted: 23 June 2021 monoclonal IGH gene rearrangement were present. HHV8 DNA was identified on plasma sample. Published: 24 June 2021 Multicentric Castleman disease in psoriatic patients is a rare event and it might be favored by the immunomodulatory treatment in longstanding psoriasis. Multicentric Castleman disease patients are Publisher’s Note: MDPI stays neutral predisposed to developing simultaneous or subsequent lymphoma. In situ mantle cell neoplasia often with regard to jurisdictional claims in behaves indolently, although it may progress to overt mantle cell lymphoma. Rituximab achieved published maps and institutional affil- a good control of psoriasis. Unfortunately, the patient developed Staphylococcus aureus sepsis for iations. which he is currently on antibiotic therapy. Keywords: psoriasis; castleman disease; HHV8; mantle cell; lymphoma; dermatopathic lympadenitis Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article A 73-year-old man presented with multiple superficial and profound lymphadenopa- distributed under the terms and thy. The patient had a 20-year history of palmoplantar psoriasis. In the last two years he conditions of the Creative Commons developed a diffuse erythrodermic picture (Figure1). Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Diagnostics 2021, 11, 1150. https://doi.org/10.3390/diagnostics11071150 https://www.mdpi.com/journal/diagnostics Diagnostics 2021, 11, 1150 2 of 5 DiagnosticsDiagnostics 20212021,, 1111,, xx FORFOR PEERPEER REVIEWREVIEW 22 ofof 55 Figure 1. Clinical image showing a diffuse erythrodermic picture of psoriasis. FigureFigure 1.1.Clinical Clinical imageimage showingshowing aa diffusediffuse erythrodermicerythrodermic picture picture of of psoriasis. psoriasis. TopicTopicTopic and andand systemic systemicsystemic medications medicationsmedications includingincludingincluding prednisolone,prprednisolone,ednisolone, acitretin,acitretin, anti-IL17anti-IL17 (ixeki- (ixek-(ixeki- izumab),zumab),zumab), TNFTNFTNF inhibitor inhibitorinhibitor (adalimumab), (adali(adalimumab),mumab), anti-IL23 anti-IL23anti-IL23 (guselkumab), (guselkumab),(guselkumab), methotrexate, methotrexate,methotrexate, cyclosporine, cyclospor-cyclospor- andine,ine, phosphodiesterase andand phosphodiesterasephosphodiesterase 4 inhibitor 44 inhibitorinhibitor (apremilast) (apremilast)(apremilast) obtained obtainedobtained little benefit. littlelittle benefit.benefit. Repeated RepeatedRepeated skin biop- skinskin siesbiopsiesbiopsies ruled ruledruled out mycosis outout mycosismycosis fungoides, fungfungoides,oides, as the asas histopathology thethe histopathologyhistopathology was consistent wawass consistentconsistent with psoriasiswithwith psoriasispsoriasis and molecularandand molecularmolecular analysis analysisanalysis excluded excludedexcluded T-cell T-cellT-cell receptor receptorreceptor (TCR) (TCR)(TCR) gene clonality.genegene clonality.clonality. TheTheThe excised excisedexcised axillary axillaryaxillary lymph lymphlymph node nodenode showed showedshowed distinctive didistinctivestinctive reactive reactivereactive features featuresfeatures of dermatopathic ofof dermato-dermato- lymphadenitispathicpathic lymphadenitislymphadenitis with paracortical withwith paracorticalparacortical hyperplasia andhyperplasiahyperplasia melanin-pigmented andand melanin-pigmentedmelanin-pigmented macrophages (Figure macro-macro-2), typicallyphagesphages (Figure(Figure seen in 2),2), chronic typicallytypically cutaneous seenseen inin inflammatory chchronicronic cutaneouscutaneous diseases. inflammatoryinflammatory diseases.diseases. Figure 2. High power view of dermatopathic lymphadenitis with melanin-laden macrophages (HE, FigureFigure 2.2.High High powerpower viewview ofof dermatopathicdermatopathic lymphadenitislymphadenitis withwith melanin-ladenmelanin-laden macrophagesmacrophages (HE,(HE, 400× magnification). 400400×× magnification).magnification). Additionally,Additionally,Additionally, atrophic, atrophic,atrophic, hyalinized hyalinizedhyalinized germinal germinalgerminal centers centerscenters with withwith prominent prominentprominent penetrating penetratingpenetrating venules ven-ven- (Figureulesules (Figure(Figure3) and 3)3) interfollicular andand interfollicularinterfollicular polytypic polytypicpolytypic plasma plasmaplasma cells were cellscells noted. werewere noted.noted. Scattered ScatteredScattered Human HumanHuman Her- pesvirusHerpesvirusHerpesvirus 8 (HHV8)-positive 88 (HHV8)-positive(HHV8)-positive cells cells (Figurecells (Figure(Figure4) within 4)4) withinwithin the mantle thethe mantlemantle and interfollicular andand interfollicularinterfollicular regions re-re- weregionsgions identified. werewere identified.identified. A subtle AA subtlesubtle rim of rimrim cyclin ofof cyclincyclin D1-positive D1-positiveD1-positive mantle mantlemantle cells was cellscells disclosed waswas discloseddisclosed within withinwithin few reactive-appearingfewfew reactive-appearingreactive-appearing follicles folliclesfollicles (Figure (Figure(Figure5). 5).5). Diagnostics 2021, 11, 1150 3 of 5 Diagnostics 2021, 11, x FOR PEER REVIEW 3 of 5 Diagnostics 2021, 11, x FOR PEER REVIEW 3 of 5 Figure 3. Hyalinized germinal centers with penetrating venules characteristic of Castleman disease Figure 3. Hyalinized germinal centers with penetrating venules characteristic of Castleman disease Figure(HE, 400× 3. Hyalinized magnification). germinal centers with penetrating venules characteristic of Castleman disease (HE,(HE, 400 400×× magnification).magnification). Figure 4. Scattered cells positive for HHV8 immunostaining (magnification 200×). FigureFigure 4. 4.Scattered Scattered cells cells positive positive for for HHV8 HHV8 immunostaining immunostaining (magnification (magnification 200 200×).×). These findings were consistent with HHV8-positive multicentric Castleman disease (MCD) of mixed type associated with in situ mantle cell neoplasia (isMCN). The transloca- tion t(11;14)(q13;q32) characteristic of mantle cell lymphoma (MCL) and the monoclonal IGH gene rearrangement were identified by fluorescence in situ hybridization (FISH) anal- ysis and molecular study, respectively. HHV8 DNA (71 copies/mL) was identified by polymerase chain reaction (PCR) on the plasma sample. Diagnostics 2021, 11, 1150 4 of 5 Diagnostics 2021, 11, x FOR PEER REVIEW 4 of 5 Figure 5. Cyclin D1-positive cells within the mantle zone of a reactive-appearing follicle (im- Figure 5. Cyclin D1-positive cells within the mantle zone of a reactive-appearing follicle (immunos- munostain, 200× magnification).
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