Mucous membrane plasmacytosis (MMP) is an uncommon variant of mucositis represented by a polyclonal plasma cell infiltration of mucosal tissue. Various clinical presentations in the upper airway have been reported ranging from erythematous mucosa to fungating masses. Histologic features include mucosal epithelial hyperplasia or psoriasiform changes with a dense submucosal infiltrate of polytypic plasma cells. Molecular studies for immunoglobulin gene rearrangement should be performed in all cases of MMP to rule out clonal neoplastic expansion of plasma cells. We present a case of MMP with over 15 years of clinical follow-up, emphasizing the relatively benign clinical course of this disorder

Brettler, Doreen B.

Chen, Benjamin J.

Hutchinson, Lloyd

Makarenko, Vladislav V.

Vaezi, Alec E.

Woda, Bruce A.

English

eScholarship@UMMS

University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2019-11-27 Laryngeal mucous membrane plasmacytosis with 15 year follow-up: Case report and literature review Vladislav V. Makarenko University of Massachusetts Medical School Et al. Let us know how access to this document benefits you. Follow this and additional works at: https://escholarship.umassmed.edu/oapubs  Part of the Hematology Commons, Hemic and Lymphatic Diseases Commons, Stomatognathic Diseases Commons, and the Tissues Commons Repository Citation Makarenko VV, Vaezi AE, Brettler DB, Hutchinson L, Woda BA, Chen BJ. (2019). Laryngeal mucous membrane plasmacytosis with 15 year follow-up: Case report and literature review. Open Access Articles. https://doi.org/10.1016/j.lrr.2019.100190. Retrieved from https://escholarship.umassmed.edu/oapubs/4131 Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License. This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact Lisa.Palmer@umassmed.edu. Contents lists available at ScienceDirectLeukemia Research Reportsjournal homepage: www.elsevier.com/locate/lrrLaryngeal mucous membrane plasmacytosis with 15 year follow-up: Casereport and literature reviewVladislav V. Makarenkoa, Alec E. Vaezib, Doreen B. Brettlerc, Lloyd Hutchinsona, Bruce A. Wodaa,Benjamin J. Chena,⁎a Department of Pathology, UMass Memorial Medical Center, Worcester, MA 01605, USAbDepartment of Otolaryngology, UMass Memorial Medical Center, Worcester, MA 01605, USAc Department of Hematology-Oncology, UMass Memorial Medical Center, Worcester, MA 01605 USAA R T I C L E I N F OKeywords:Mucous membrane plasmacytosisLong-term follow-upA B S T R A C TMucous membrane plasmacytosis (MMP) is an uncommon variant of mucositis represented by a polyclonalplasma cell inﬁltration of mucosal tissue. Various clinical presentations in the upper airway have been reportedranging from erythematous mucosa to fungating masses. Histologic features include mucosal epithelial hyper-plasia or psoriasiform changes with a dense submucosal inﬁltrate of polytypic plasma cells. Molecular studies forimmunoglobulin gene rearrangement should be performed in all cases of MMP to rule out clonal neoplasticexpansion of plasma cells. We present a case of MMP with over 15 years of clinical follow-up, emphasizing therelatively benign clinical course of this disorder.1. IntroductionMucous membrane plasmacytosis (MMP) is a rare variant of mu-cositis represented by a polyclonal plasma cell inﬁltration of the tissue.The diagnosis can be challenging considering signiﬁcant histologicalsimilarities with neoplastic lesions. About 50 cases have been reportedin the English literature including less than 10 published cases withlong (more than 5 years) follow-up [1–6]. The ﬁrst evidence of unusualplasma cell inﬁltrate was described in glans penis by Zoon in 1952which he termed a “chronic benign balanoposthitis with plasmacytes”[7]. Clinicopathologically similar process was later identiﬁed in or-ofacial mucosa by Schuermann [8] and Luders [9], and was originallynamed plasmacytosis circumﬁcialis. Since then, multiple terms wereintroduced including plasmacytosis mucosae, plasma cell oriﬁcial mu-cositis, plasma cell mucositis, and MMP, however no consensus in ter-minology still exists. Exceedingly rare cases of cutaneous and systemicvariants of plasmacytosis have been reported in patients of Asian des-cent but appear to be unrelated to MMP [10].The etiology of MMP is not clear, but associations with some exo-genous factors or immunologically mediated diseases were suggested[2]. Recognition of the entity is important as no progression to plasmacell or other hematological neoplasm was noted. Only one reported caseshowed concomitant squamous cell carcinoma with unclear etio-pathogenetic association [11]. The median age of the patients atpresentation is 60 years old and ranging from 17 to 84 years old.Various clinical presentations have been reported ranging from er-ythematous surface of mucosa to fungating mass. The major histologicalfeatures include epithelial hyperplasia or psoriasiform changes with adense inﬁltrate of polytypic plasma cells. The plasma cells can presentwith occasional Russel bodies but show no atypia. Molecular studies forimmunoglobulin (Ig) gene rearrangement should be performed in allcases of MMP to rule out clonal expansion of plasma cells. Here wepresent a rare case of MMP with over 15 years follow-up.2. Case reportWe report a case of a 68-year-old female with a history of chronicobstructive pulmonary disease and smoking, who presented with a longhistory of dysphagia due to a persistent laryngeal lesion, ﬁrst identiﬁedin 2002. A biopsy of the laryngeal lesion in 2002 showed a submucosalplasmacytosis. Deﬁnitive evidence of clonality was not seen by im-munohistochemical (IHC) or molecular testing. The patient had normalimmunoglobulin levels and serum protein immunoﬁxation was nega-tive for monoclonal proteins. Complete blood count and chemistry testswere within normal limits. Serum protein studies showed free kappaand lambda light a chain within normal limits, no monotypic im-munoglobulin band on immunoﬁxation electrophoresis was seen. Noadditional masses were identiﬁed. The patient had localized cervicalhttps://doi.org/10.1016/j.lrr.2019.100190Received 14 March 2019; Received in revised form 13 November 2019; Accepted 23 November 2019⁎ Corresponding author. Current aﬃliation. Bristol-Myers Squibb, Cambridge, MA, USA.E-mail address: benjamin.chen@bms.com (B.J. Chen).Leukemia Research Reports 13 (2020) 100190Available online 27 November 20192213-0489/ © 2019 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).Tlymphadenopathy in 2002 that was biopsied to reveal a benign reactivelymph node. The patient was treated with low dose prednisone whichrelieved the dysphagia in 2002. The patient experienced a waxing andwaning course over the next 15 years that was fairly responsive tosteroid therapy. She recently re-presented in 2017 with mild enlarge-ment of a papillomatous laryngeal lesion, no monotypic im-munoglobulin band on immunoﬁxation electrophoresis was seen, and arepeat biopsy of the lesion was performed.The histological ﬁndings were similar between the 2002 and 2017biopsy. The sections from the laryngeal biopsies showed squamousmucosa with nodular psoriasiform epithelial hyperplasia (Fig. 1). Nodysplasia was seen. There was neutrophilic inﬂammation of the epi-thelium with occasional microabscesses. A prominent, dense, sub-mucosal inﬁltrate composed primarily of plasma cells was present.Plasma cells appeared mature with round nuclei and without prominentnucleoli. IHC studies showed that the plasma cells were positive forCD138 (variable expression) and CD38; and negative for CD56, CD20,cyclin D1 and HHV8 (Fig. 2). Kappa and lambda IHC and in-situ hy-bridization (ISH) studies showed elevated kappa:lambda ratio, but de-ﬁnitive evidence of monotypic light chain expression was not seen.EBER ISH was negative. Grocott's methenamine silver (GMS) andspirochete stains were negative for microorganisms. Molecular PCRstudies performed in 2002 were negative for clonal immunoglobulinheavy chain (IGH) gene rearrangements. In the biopsy from 2017, PCRstudies showed an equivocal gene rearrangement of the IGH gene in apolyclonal background, and no clonal rearrangements of IGK, IGL, andIGK deleting element.3. DiscussionFew reports are available regarding long-term histopathological andclinical follow-up of mucous membrane plasmacytosis (MMP). InFig. 1. Hematoxylin-eosin stain demonstrating hyperplastic epithelium with plasma cells rich underlying lamina propria. A. (× 100 magniﬁcation). B. Prominent,dense, subepithelial inﬁltrate composed primarily of mature plasma cells without atypia and rare Russel bodies (× 400 magniﬁcation).Fig. 2. Selected immunohistochemical stains demonstrated in tumor cells. Positive staining for CD138 and CD38, and negative staining for CD20, CD56, Cyclin D1and HHV8. (× 200 magniﬁcation).V.V. Makarenko, et al. Leukemia Research Reports 13 (2020) 1001902Table1Summaryofreportedcasesofmucousmembraneplasmacytosis.CaseAge(years),genderLocationPresumableetiologicalfactorHistologicﬁndingsAncillarystudiesFollowupWhiteetal.,198647,Flips,mouth,tongue,supraglotticlarynxSmokerfor32yearsEpidermalacanthosiswithintercellularedema,milddyskeratosisandexocytosis;densebandlikeinﬁltrateofplasmacellsintheupperdermisStainedpolytypicforκandλlightchainsaswellasßandγheavychainsPersistentdisease,9yrsTimmsMSetal.,199132,Fsupraglottis,gingiva,mucobuccalNotreportedMarkedpseudoepitheliomatoushyperplasiawithdense,predominantlyplasmacyticinﬁltrationofthelaminapropria;theplasmacellsarematureandlackedpleomorphismStainedpolytypicforκandλlightchainsandvariousheavychainsPersistentdisease,7yGrattanetal.,199268,MpapillaryhyperplasiaextendingfromthehardpalatetotheuvulaLong-termdenturesHyperplasticepitheliumwithadiﬀuseinﬁltrateofneutrophilsinthedeeperlayersformingspongiformmicro-abscessesinthesubcornealregion;denseinﬂammatoryinﬁltrateinthelaminapropriaconsistingalmostentirelyofmatureplasmacells.StainedpolytypicforIgG;PASandGMSstainswerenegativeforfungi.Persistentdisease,15yFerreiroetal.,199441,FSupraglottic,glotticlarynx,nose,pharynxNotreportedPsoriasiformchangeswithparakeratosis,elongationofreteridges,suprapapillalryepithelialthinning.Markeddyskeratosis.DispersedexocytosisandaggregationofPMNswiththeepidermis.Munro-microabscesslikelesionsin2cases.DiﬀuseexpanseofinﬂammatorycellsinsubmucosaltissuecomposedlargelyofmatureplasmacellswithscatteredPMNsandlymphocytes.Foamymacrophagesarenotpresent.Theplasmacellsdidnotshowanaplasia,prominentnucleoliorDutcherbody.OccasionalRusselbodiesarepresent.Noassociatedendothelialhyperplasia.Stainedpolytypicforκandλlightchains.OnlyonecasewasstudiedandfoundtobenegativeforgenerearrangementinIg-encodingregion.Warthin-Starry,GMS,Grammstainswerenegativeformicroorganisms.Persistentdisease,7y,tracheostomy62,FSupraglottic,glotticlarynx,tracheaNotreportedPersistentdisease,16y,tracheostomy45,FSupraglotticlarynx,lips,mouth,tongueNotreportedPersistentdisease,9y40,MSupraglottic,glotticlarynx,lips,mouth,tongue,palate,pharynxNotreportedPersistentdisease,15years,apneaFogartyetal.200127,FGingivaprogressedtosupraglotticandglotticlarynxChewinggumPseudo-epitheliomatoushyperplasiaofthesurfaceepithelium,withadenselycellularinﬁltrate,almostentirelyplasmacytic.TheIHCrevealedsmallamountsofIgA,abundantIgG.Stainedpolytypicforκandλlightchains.Persistentdisease,21yGalvinetal.,201668FGingivalLong-termdenturesPartlyulceratedsquamousepitheliumwithanunderlyingdensepolyclonalplasmacellinﬁltrate.Nointerfacemucositiswasseen.Stainedpolytypicforκandλlightchains.Remissionfor7y69,MOropharynxNotreportedPolyclonalplasmacyticinﬂammatoryinﬁltratethroughouttheconnectivetissue.Persistentdisease,10y,recentﬂareOurcase53,FSupraglottic,glotticlarynxSmokerforover20yearsStainedpolytypicforκandλlightchains;negativeforgenerearrangementinIg-encodingregion.Warthin-Starry,GMS,Grammstainswerenegativeformicroorganisms.Persistentdisease,15yV.V. Makarenko, et al. Leukemia Research Reports 13 (2020) 1001903Table 1, we summarized all such cases published in English literature.The median age at presentation was 46 years old and ranging from 27to 69 years old. We found that this age range is signiﬁcantly lesscompared to short-term follow-up cases of MMP. It can be explained byquicker loss of follow-up in older population due to comorbidities. Nodeference was found in gender predilection in long-term vs short-termfollow-up cases. The clinical course of MMP is typically waxing andwaning with periods of long remissions. Progression to loss of organfunctions in treatment-resistant cases is not uncommon. Histologicalrepresentation of cases with long-term follow-up shows a few dis-tinctive features that are discussed in greater details further. There is noconsensus on the treatment for MMP; it includes steroids as ﬁrst-linetherapy and various topical or systemic immunosuppressive agents, i.e.tacrolimus, cyclosporin, methotrexate, chlorambucil, and dapsone[2,12,13]. Low-dose radiotherapy was also reported [1].The etiological factors of MMP are still not clear, but role of exo-genous factors was suggested based on possible association withsmoking and long-term use of dentures [5]. On the other hand, anumber of MMP patient with autoimmune or immune-mediated diseasewere observed suggesting a possible implication by the systemic pro-cesses [2,14]. Gross presentation of MMP shows signiﬁcant variationand includes papillomatous, cobblestone, nodular, or granulomatousmucosa and sometimes hyperplastic proliferation of mucosa resulting infungating ulcerated mass. The later can grossly mimic squamous cellcarcinoma (SSC). Considering commonly found ﬂorid pseudo-epithe-liomatous hyperplasia in overlying epithelium of MMP, serious cautionshould be taken when evaluating such cases. Only one case of MMPwith associated invasive SSC was reported in an ex-smoker patient witha history of chemotherapy [11]. Other clinical diﬀerential diagnosiscommonly includes lichen planus, lymphoproliferative disorders, in-fection, sarcoidosis, and granulomatosis with polyangiitis. Close histo-pathological examination is important to rule out most of these con-ditions. Rhinoscleroma can be considered in diﬀerential diagnosis sinceit can present with hyperplastic mucosa with inﬂammatory inﬁltratewith abundant plasma cells. However, vasculitis is commonly seen inrhinoscleroma, and foamy macrophages with gram negative bacteria,conﬁrmed by special stains are diagnostic. Plasma cell gingivitis showssimilar histological features, but it is a localized hypersensitivity reac-tion to oﬀending agents, which typically resolves after their removal,thus conﬁrming the diagnosis clinically [15].Most diagnostic challenges of MMP arise from its histologic simi-larities with plasma cell neoplasm and lymphomas that can also man-ifest as dense inﬁltrate of plasmocytoid cells in the lamina propria.Thus, Ig clonality studies are warranted for appropriate diagnosis.Virtually all cases with long-standing history of MMP and treatmentresistance develop signiﬁcant changes in overlying epithelium in-cluding pseudo-epitheliomatous and/or psoriasiform changes.Interestingly, dyskeratosis in the absence of other Bowenoid featureshave been frequently reported. Secondary reactive changes in epithe-lium could be seen and include mixed inﬂammatory inﬁltrate,polymorphonuclear leukocyte exocytosis and even intraepithelial mi-croabscess formation. The plasma cells in MMP usually do not showatypical features such as prominent nucleoli or Dutcher bodies, butRussel bodies are not uncommon. Plasma cells stain positive for CD138and CD38 without expression of aberrant markers such as CD56. It isreasonable to assess tissues for HHV8 since mixed inﬂammatory in-ﬁltrate enriched by polytypic plasma cells can be seen in Kaposi sar-coma. As noted before, it is important to assess polyclonal nature ofplasma cell inﬁltrate by surface Ig immunochemical stains or in-situhybridization. The most reliable study to evaluate clonality is Ig generearrangements by PCR. Only very few reported cases of MMP in-cluding ours were assessed by clonality studies. Interpretation ofplasma cell clonality by Ig gene rearrangement can be challengingconsidering presence of non-speciﬁc pick(-s) in reactive polyclonalbackground especially in long-standing MMP. These cases should bereassessed by comparing sub-clones from previous biopsies.To conclude, nearly all reported cases of CP have required multiplebiopsies and numerous additional studies before a deﬁnitive diagnosiscould be achieved. Clinicopathological correlation is crucial in con-ﬁrming the diagnosis.References[1] G. Fogarty, H. Turner, J. Corry, Plasma cell inﬁltration of the upper aerodigestivetract treated with radiation therapy, J. Laryngol. Otol. 115 (11) (2001) 928–930.[2] S. Galvin, et al., Circumoriﬁcial plasmacytosis/plasma cell oriﬁcial mucositis: a caseseries and a review of the literature, Oral Surg. Oral Med. Oral Pathol. Oral Radiol.122 (3) (2016) e77–e81.[3] J.W. White Jr., K.D. Olsen, P.M. Banks, Plasma cell oriﬁcial mucositis. Report of acase and review of the literature, Arch Dermatol. 122 (11) (1986) 1321–1324.[4] M.S. Timms, P. Sloan, Association of supraglottic and gingival idiopathic plasma-cytosis, Oral Surg. Oral Med. Oral Pathol. 71 (4) (1991) 451–453.[5] C.E. Grattan, T.A. Gentle, M.K. Basu, Oral papillary plasmacytosis resemblingcandidosis without demonstrable fungus in lesional tissue, Clin. Exp. Dermatol. 17(2) (1992) 112–116.[6] J.A. Ferreiro, et al., Mucous membrane plasmacytosis of the upper aerodigestivetract. A clinicopathologic study, Am. J. Surg. Pathol. 18 (10) (1994) 1048–1053.[[7]] J.J. Zoon, [Chronic benign circumscript plasmocytic balanoposthitis],Dermatologica 105 (1) (1952) 1–7.[8] H. Schuermann, Plasmacytosis circumoriﬁcialis, Dtsch. Zahnarztl. (15) (1960)601–610.[[9]] G. Luders, Plasmocytosis mucosae: ein oft verkanntes neues Krankheitsbild,Munch Ed Wochenschr (114) (1972) 8–12.[10] C. Georgesen, M. Kheterpal, M. Pulitzer, A rare case of cutaneous plasmacytosis in aKorean male, Case Rep. Pathol. 2017 (2017) 3032941.[11] T. Pepper, et al., Squamous cell carcinoma arising in mucosal plasmacytosis, Br. J.Oral Maxillofac. Surg. 48 (3) (2010) 208–210.[12] N.A. Khan, W.S. McKerrow, T.J. Palmer, Mucous membrane plasmacytosis of theupper aerodigestive tract. A case report with eﬀective treatment, J. Laryngol. Otol.111 (3) (1997) 293–295.[13] R. Bharti, D.R. Smith, Mucous membrane plasmacytosis: a case report and review ofthe literature, Dermatol. Online J. 9 (5) (2003) 15.[14] L.W. Solomon, et al., Plasma cell mucositis of the oral cavity: report of a case andreview of the literature, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 106(6) (2008) 853–860.[15] S. Silverman Jr., F. Lozada, An epilogue to plasma-cell gingivostomatitis (allergicgingivostamtitis), Oral Surg. Oral Med. Oral Pathol. 43 (2) (1977) 211–217.V.V. Makarenko, et al. Leukemia Research Reports 13 (2020) 1001904

Laryngeal mucous membrane plasmacytosis with 15 year follow-up: Case report and literature review

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Laryngeal mucous membrane plasmacytosis with 15 year follow-up: Case report and literature review

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