Case report In of 2014 August, a 54-year-old man offered a several-month history of nontender, nonpruritic well-circumscribed erythematous plaques on his temples. The individual was feeling well without constitutional symptoms in any other case. A biopsy at that ideal period discovered a harmless lymphocytic infiltrate in keeping with pseudolymphoma. Extra evaluation with bloodstream work and imaging was advised but not completed by the patient as he stated the lesions self-resolved. In June 2017, the patient returned to the clinic with similar lesions on the temples with additional widespread, asymptomatic erythematous papules on the trunk and lower extremities (Fig 1, em A /em ). The patient was otherwise feeling well and denied any constitutional symptoms. Open in a separate window Fig 1 Patient observed initially (A) and 5?months after consolidation therapy (B). Three skin biopsy specimens were taken from the left central temple, the left lower back, and right medial distal pretibial region (Fig 2). Histopathologic examination found intact lymphocytes and plasma cells within the cytoplasm of histiocytes (emperipolesis). Immunohistochemically, the histiocytes were positive for CD68 and CD163 with coexpression of S100. Based on the clinical and histopathologic findings, a diagnosis of Rosai-Dorfman was made. Open in a separate window Fig 2 A, Biopsy findings show a diffuse infiltrate of mononuclear cells with abundant pale cytoplasm in the papillary dermis. B, On higher power, histiocytes with abundant cytoplasm and conspicuous nucleoli ( em red arrows /em ) and emperiopolesis of lymphocytes and neutrophils ( em black arrows /em ) have emerged. C, S100+ staining of histiocytes. D, Higher-power look at of S100+ histiocytes with adverse staining of intracytoplasmic hematolymphoid cells ( em arrows /em ). Laboratory evaluation found out a normocytic anemia (hemoglobin, 12.4?g/dL), eosinophilia (11%), and peripheral blood circulation cytometry teaching excess polyclonal IgA and IgG. A total-body competed tomography check out found intensive lymphadenopathy inside the upper body, abdominal, retroperitoneum, and pelvis; severe splenomegaly moderately; a mural mass in the sigmoid digestive tract; and gentle pulmonary nodularity in the remaining lower lobe. Bone tissue lymph and marrow node biopsies were performed and were in keeping with mantle cell non-Hodgkin lymphoma stage IVa. The individual was signed up for a clinical trial at MD Anderson Medical center for even more treatment, which involved ibrutinib/rituximab and hyperCVAD for consolidation (fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone). Two cycles of therapy led to a marked reduction in his amount of skin damage (Fig 1, em B /em ) and quality of his wide-spread lymphadenopathy. The individual has remained free from constitutional symptoms. Discussion SHML or RDD was initially described in 1969, since then a lot more than 400 instances have already been reported in the RDD registry.1, 6 This disease is normally seen in kids and adults having a predilection for white men and the ones of African descent.6 RDD is a rare entity; even rarer are reports of concomitant lymphoma. This report is the first, to our knowledge, to demonstrate RDD with concomitant mantle cell lymphoma. After reviewing the relevant literature, we found 25 cases of RDD in association with Hodgkin and non-Hodgkin lymphoma; of these, most of these cases (70%) had simultaneous diagnosis of RDD and lymphoma (Table I).3, 4, 5 The pathogenesis of RDD is unclear. Suggested possibilities include a macrophage colony stimulating factor resulting Plau in immune-suppressive abnormal histiocytes (an immune-related phenomenon), an exaggerated infectious response to an agent (both viral and bacterial), and/or a genetic predisposition.2, 21 Our patient’s concurrent diagnosis of mantle cell lymphoma after his diagnosis of RDD, and the observation that consolidation therapy of his lymphoma resulted in improvement of his RDD, lends support for the possible immune-mediated etiology of RDD. Table I Cases of RDD and malignant lymphoma thead th rowspan=”1″ colspan=”1″ Case no. /th th rowspan=”1″ colspan=”1″ Reference /th th rowspan=”1″ colspan=”1″ Age/sex /th th rowspan=”1″ colspan=”1″ Lymphoma type /th th rowspan=”1″ colspan=”1″ Period period /th /thead 1Foucar et?al,7 19836/MLarge cell immunoblasticNHL 8?mo after RDD2Rangwala et?al,8 199062/MSmall noncleavedNHL 4?con after RDD3Falk et?al,9 199149/MHD, MCConcurrent424/MHD, NOSConcurrent5Maia et?al,10 199539/MHD, LPConcurrent611/MHD, LPConcurrent7Koduru et?al,11 199552/MT cellNHL 8?con after RDD8Alliot et?al,12 1996UnknownHD, NOSHD before RDD9Krzemieniecki et?al,13 199617/FHigh quality, NOSNHL 5?con after RDD10Lossos et?al,14 199767/MSmall lymphocyticNHL 12?con before RDD11Lu et?al,15 200062/FFL quality IIConcurrent1230/FHD, LPConcurrent1328/MHD, LPConcurrent1463/FFL quality Sitagliptin phosphate distributor IConcurrent15Menzel et?al,16 2003?/FNHL, NOSNHL 6?con before RDD16Garel et?al,17 20048/FAnaplastic huge cellConcurrent17Shoda et?al,18 200464/MDiffuse huge B cellConcurrent18Moore et?al,2 200833/FDiffuse large B cellConcurrent19Luca Di Tommaso et?al,19 201065/FRelapsed FLConcurrent20Cvetkovic et?al,20 201039/FHD, NSHD 2?y after RDD21Pang et?al,21 201180/FNodal MZLConcurrent22Wu et?al,22 201242/MDiffuse large B cellConcurrent23Akria et?al,3 201350/MNodal MZLConcurrent24Fernandez-Vega et?al,4 201451/FHD, NSConcurrent25Garg et?al,5 201716/MAnaplastic large cellConcurrent26Present case54/MNHL, mantle cellConcurrent Open in a separate window em FL /em , Follicular lymphoma; em HD /em , Hodgkin disease; em LP /em , lymphocyte predominant; em MC /em , mixed cellularity; em MZL /em , marginal zone lymphoma; em NHL /em , non-Hodgkin lymphoma; em NOS /em , not otherwise specified; em NS /em , nodular sclerosis. em Note /em . Table was produced/adapted by Akria et?al3 with additional cases added since their publication in 2013. Footnotes Funding sources: None. Conflicts of interest: None disclosed.. involvement without constitutional symptoms. Case statement In August of 2014, a 54-year-old man presented with a several-month Sitagliptin phosphate distributor history of nontender, nonpruritic well-circumscribed erythematous plaques on his temples. The patient was otherwise feeling well without constitutional symptoms. A biopsy at that time found a benign lymphocytic infiltrate consistent with pseudolymphoma. Additional evaluation with blood work and imaging was advised but not completed by the patient as he stated the lesions self-resolved. In June 2017, the patient returned to the medical center with equivalent lesions in the temples with extra popular, asymptomatic erythematous papules in the trunk and lower extremities (Fig 1, em A /em ). The individual was otherwise sense well and rejected any constitutional symptoms. Open up in another home window Fig 1 Individual observed originally (A) and 5?a few months after loan consolidation therapy (B). Three epidermis biopsy specimens had been extracted from the still left central temple, the still left back, and best medial distal pretibial area (Fig 2). Histopathologic evaluation found unchanged lymphocytes and plasma cells inside the cytoplasm of histiocytes (emperipolesis). Immunohistochemically, the histiocytes had been positive for Compact disc68 and Compact disc163 with coexpression of S100. Predicated on the scientific and histopathologic results, a medical diagnosis of Rosai-Dorfman was produced. Open in another home window Fig 2 A, Biopsy results present a diffuse infiltrate of mononuclear Sitagliptin phosphate distributor cells with abundant pale cytoplasm in the papillary dermis. B, On higher power, histiocytes with abundant cytoplasm and conspicuous nucleoli ( em crimson arrows /em ) and emperiopolesis of lymphocytes and neutrophils ( em dark arrows /em ) have emerged. C, S100+ staining of histiocytes. D, Higher-power watch of S100+ histiocytes with harmful staining of intracytoplasmic hematolymphoid cells ( em arrows /em ). Lab evaluation discovered a normocytic anemia (hemoglobin, 12.4?g/dL), eosinophilia (11%), and peripheral blood circulation cytometry showing surplus polyclonal IgG and IgA. A total-body competed tomography check found comprehensive lymphadenopathy inside the upper body, abdominal, retroperitoneum, and pelvis; reasonably serious splenomegaly; a mural mass in the sigmoid digestive tract; and minor pulmonary nodularity in the still left lower lobe. Bone tissue marrow and lymph node biopsies had been performed and had been in keeping with mantle cell non-Hodgkin lymphoma stage IVa. The individual was signed up for a scientific trial at MD Anderson Hospital for further treatment, which involved ibrutinib/rituximab and hyperCVAD for consolidation (fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone). Two cycles of therapy led to a marked reduction in his variety of skin damage (Fig 1, em B /em ) and quality of his popular lymphadenopathy. The individual has remained free from constitutional symptoms. Debate SHML or RDD was initially defined in 1969, since then a Sitagliptin phosphate distributor lot more than 400 situations have already been reported in the RDD registry.1, 6 This disease is normally seen in kids and young adults having a predilection for white males and those of African descent.6 RDD is a rare entity; actually rarer are reports of concomitant lymphoma. This statement is the 1st, to our knowledge, to demonstrate RDD with concomitant mantle cell lymphoma. After critiquing the relevant literature, we found 25 instances of RDD in association with Hodgkin and non-Hodgkin lymphoma; of these, most of these instances (70%) experienced simultaneous analysis of RDD and lymphoma (Table I).3, 4, 5 The pathogenesis of RDD is unclear. Suggested options include a macrophage colony revitalizing factor resulting in immune-suppressive irregular histiocytes (an immune-related trend), an exaggerated infectious response to an agent (both viral and bacterial), and/or a genetic predisposition.2, 21 Our patient’s concurrent analysis of mantle cell lymphoma after his analysis of RDD, and the observation that consolidation therapy of his lymphoma resulted in improvement of his RDD, lends support for the possible immune-mediated etiology of RDD. Table I Instances of RDD and malignant lymphoma thead th rowspan=”1″ colspan=”1″ Case no. /th th rowspan=”1″ colspan=”1″ Research /th th rowspan=”1″ colspan=”1″ Age/sex /th th rowspan=”1″ colspan=”1″ Lymphoma type /th th rowspan=”1″ colspan=”1″ Time interval /th /thead 1Foucar et?al,7 19836/MLarge cell immunoblasticNHL 8?mo after RDD2Rangwala et?al,8 199062/MSmall noncleavedNHL 4?y after RDD3Falk et?al,9 199149/MHD, MCConcurrent424/MHD, NOSConcurrent5Maia et?al,10 199539/MHD, LPConcurrent611/MHD, LPConcurrent7Koduru et?al,11 199552/MT cellNHL 8?y after RDD8Alliot et?al,12 1996UnknownHD, NOSHD before RDD9Krzemieniecki et?al,13 199617/FHigh grade, NOSNHL 5?y after RDD10Lossos et?al,14 199767/MSmall lymphocyticNHL 12?y before RDD11Lu et?al,15 200062/FFL grade IIConcurrent1230/FHD, LPConcurrent1328/MHD, LPConcurrent1463/FFL grade IConcurrent15Menzel et?al,16 2003?/FNHL, NOSNHL 6?y before RDD16Garel et?al,17 20048/FAnaplastic large cellConcurrent17Shoda et?al,18 200464/MDiffuse large B cellConcurrent18Moore et?al,2 200833/FDiffuse large B cellConcurrent19Luca Di Tommaso et?al,19 201065/FRelapsed FLConcurrent20Cvetkovic et?al,20 201039/FHD, NSHD 2?y after RDD21Pang et?al,21 201180/FNodal MZLConcurrent22Wu Sitagliptin phosphate distributor et?al,22 201242/MDiffuse large B cellConcurrent23Akria et?al,3 201350/MNodal MZLConcurrent24Fernandez-Vega et?al,4 201451/FHD, NSConcurrent25Garg et?al,5 201716/MAnaplastic large cellConcurrent26Present case54/MNHL, mantle cellConcurrent Open in a separate windowpane em FL /em , Follicular lymphoma; em HD /em , Hodgkin disease; em LP /em , lymphocyte predominant; em MC /em , blended cellularity; em MZL /em , marginal area lymphoma; em NHL /em , non-Hodgkin lymphoma; em NOS /em , not really otherwise given; em NS /em , nodular sclerosis. em Take note /em . Desk was made/modified by Akria et?al3 with additional situations added since their publication in 2013. Footnotes Financing sources: None. Issues appealing: non-e disclosed..