J Cutan Pathol 2014: 41: 625–629doi: 10.1111/cup.12375John Wiley & Sons. Printed in Singapore

© 2014 John Wiley & Sons A/S.Published by John Wiley & Sons Ltd

Journal ofCutaneous Pathology

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Lauren N Stuart MD, MBA1, Kim M Hiatt MD2, Zohreh Zaki MD3, Jerad M Gardner MD4 and Sara C ShalinMD, PhD4

Figures 1 and 2 are depicted on the journal cover.

Figure 5.

Figure 4.

Figure 3.

Figure 6.

Your diagnosis?

Discussion follows on page 626

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Plaque-like CD34-Positive DermalFibroma/Medallion-like DermalDendrocyte Hamartoma: An UnusualSpindle Cell Neoplasm

Lauren N Stuart MD, MBA1, Kim M Hiatt MD2, Zohreh Zaki MD3, Jerad M Gardner MD4

and Sara C Shalin MD, PhD4

1Emory University, Atlanta, GA,2DermLogic PLLC, North Little Rock, AR,

3Peninsula Regional Medical Center, Salisbury, MD, and4University of Arkansas for Medical Sciences, Little Rock, AR

Sara C Shalin, MD, PhDUniversity of Arkansas for Medical Sciences

Department of Dermatopathology4301 West Markham, #517

Little Rock, AR 72205Phone: (501) 686-8007

Fax: (501) 296-1184email: scshalin@gmail.com

Keywords: CD34, fibroblastic connective tissue nevus, medallion-like dermal dendrocyte hamartoma, spindle cell neoplasmAccepted for publication June 21, 2014

Plaque-like CD34-positive dermal fibroma,also known as medallion-like dermal den-drocyte hamartoma (MDDH), is a rare,cutaneous neoplasm that was first describedby Rodriguez-Jurado et al in 2004.1 The seminalreport described three women who presentedwith a single, distinct, congenital lesion on theneck or upper trunk. Microscopically, the tumorswere characterized by a dermal spindle cell pro-liferation that was positive for CD34 and factorXIIIa by immunohistochemistry. Immunohisto-chemical and ultrastructural studies suggestedthat the tumor was of dermal dendritic celllineage, and the authors believed this repre-sented a hamartomatous proliferation. Given itscharacteristic shape and location, the authorschose the name medallion-like dermal dendrocytehamartoma. However, further studies have sug-gested the lesion is not a hamartoma nor doesit possess dermal dendrocytic differentiation.2For these reasons, Kutzner and colleagues havesuggested the name plaque-like CD34-positivedermal fibroma.2

Herein, we describe a case encountered inconsultation. A 17-year-old female presentedto the emergency department with a recentlyenlarging lesion on the posterior neck. Theduration and any additional clinical historywere unavailable. A biopsy revealed an ele-vated nodular lesion composed of a spindlecell proliferation coursing through the mid- toupper reticular dermis but somewhat sparingthe papillary dermis (Fig. 1–3). In one area,the proliferation spread downward and focallyextended to the subcutaneous fat. The neoplas-tic cells were arranged concentrically aroundvessels and adnexal structures, thereby impart-ing a vaguely storiform pattern (Fig. 4, 5a). Onhigh power magnification, the cells displayedminimal nuclear atypia and exhibited a lowmitotic index (Fig. 6). The underlying stromawas notable for dilated vessels and occasionalmast cells, and adipose tissue was not noted tobe misplaced in the reticular dermis.

Immunohistochemical studies were per-formed to better characterize the tumor. The

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Fig. 1. Low magnification reveals a dermal proliferation ofspindled cells occupying the reticular dermis but sparing thepapillary dermis.

Fig. 2. CD34 immunostaining highlights a band-like prolifera-tion of spindle cells coursing through the reticular dermis andtracking down adnexal structures.

neoplastic cells were diffusely and stronglypositive for CD34 (Fig. 2, 5b). Rare scat-tered cells were positive for factor XIIIa,while stains for S-100 protein, Melan-A, andsmooth muscle actin were negative (notshown). Expression of the COL1A1-PDGFBfusion protein was not detected by multiplexreverse transcription-polymerase chain reaction(RT-PCR) testing. Taken together, the mor-phologic, immunophenotypic, and molecularfindings were felt to be most consistent withplaque-like CD34-positive dermal fibroma.

This entity represents a relatively newlydescribed cutaneous spindle cell neoplasmthat follows a benign clinical course.1–8 Initialstudies suggested a hamartomatous proliferationof dermal dendritic cells, hence the designationMDDH. However, additional investigation didnot support these claims, leading to a proposal

for an adjustment in nomenclature.2 Classi-cally, plaque-like CD34-positive dermal fibromapresents as a congenital, asymptomatic, soli-tary, round- or triangular-shaped lesion on theneck or trunk of young women. The overlyingskin may be pink-brown, finely-wrinkled, and/oratrophic. On microscopic examination, there is aband-like proliferation of spindle cells set withina myxoid, vascular-rich stroma. Of note, allcases described to date have shown a plaque-likeconfiguration, in distinct contrast to the ele-vated profile seen in our case. The proliferationis typically present within the upper reticulardermis but in some instances can extend intothe subcutaneous fat.1,2,5–7 The neoplastic cellsare arranged in a vaguely storiform pattern,due to their concentric arrangement aroundvessels and peripheral nerves. Cytologically, thecells are bland and have inconspicuous nucleoli.Mitoses should be scant (fewer than one per10 high power fields). Other described findingsinclude increased mast cells and fragmentedelastic fibers. Immunohistochemically, the neo-plastic cells are positive for CD34, fascin, andvimentin but are negative for S-100 protein,CD1a, and CD68. Although the original caseseries suggested that factor XIIIa was a markerfor plaque-like CD34-positive dermal fibroma,this finding has been inconsistent in subsequentreports.2,5,8

To date, only 17 cases have been reported inthe literature, and thus the tumor is probablynot yet fully characterized.1–8 Recently, Kutznerand colleagues have suggested an expansionof the clinicopathologic criteria for plaque-likeCD34-positive dermal fibroma. Five additionalcases were presented, all of which presentedas asymptomatic dermal plaques composed ofCD34-positive dermal spindled cells. However,four of five presented clinically as lesions thatwere neither congenital nor located on theneck or trunk but rather as acquired tumorson the extremities. Despite this variation, allcases exhibited a similar immunohistochemicalprofile and followed a benign clinical course.Based on these findings, the authors suggestedthat these lesions were related and should all beconsidered the same entity.2

The histopathologic and clinical differentialdiagnosis of plaque-like CD34-positive dermalfibroma is broad and can depend, in large part,upon the clinical presentation. An atrophiclesion may be mistaken clinically for aplasiacutis.1,4–6,8 Other cases in the literature havebeen misdiagnosed clinically as melanocyticnevus, dermatofibroma, and lichen planus-like

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keratosis. However, these diagnoses are easilyruled out upon microscopic examination.

Perhaps most closely related microscopic dif-ferential diagnosis to the presently describedcase is the fibroblastic connective tissue nevus(FCTN). Arising in a similar patient demo-graphic, FCTN may (as in our case) have a pro-tuberant rather than plaque-like appearance onlow power magnification.9 However, FCTN is typ-ically centered more deeply in the dermis, withmisplaced adipose tissue present in the reticulardermis and entrapment of appendages and colla-gen bundles by the lesional cells. Like plaque-likeCD34-positive dermal fibroma, FCTN is com-posed of a dermal proliferation of CD34-positivespindled cells, but the pattern of expressionis typically patchy and weak whereas it is dif-fusely strong in plaque-like CD34-positive dermalfibroma.9

Plaque-like CD34-positive dermal fibroma canbe mistaken for a number of other dermal spin-dle cell neoplasms, such as a dermatomyofi-broma, a non-pigmented cellular blue nevus, ora diffuse neurofibroma.2,7 However, the first twoentities lack CD34 immunoreactivity and the lat-ter two will express S-100 protein. Furthermore,architecture may be of help in distinguishingbetween these neoplasms. The cells of dermato-myofibroma will be arranged in fascicles parallelto the epidermis rather than the vague stori-form pattern of plaque-like CD34-positive der-mal fibroma, while a neurofibroma classically haswavy cells and nuclei.

Lastly and importantly, a dermal based pro-liferation of CD34-positive spindled cells in avaguely storiform pattern may lead one to con-sider dermatofibrosarcoma protuberans (DFSP)within the histopathologic differential diagno-sis. This may be especially relevant in cases ofplaque-like CD34-positive dermal fibroma whichinvolve the underlying subcutaneous fat, a find-ing which simulates the characteristic ‘fat trap-ping’ of DFSP. Distinguishing between thesetwo entities is of great importance due to dif-fering biologic behavior and consequent treat-ment recommendations. Whereas plaque-likeCD34-positive dermal fibroma can be treatedwith conservative excision, DFSP requires Mohsmicrographic surgery or wide-local excision dueto its locally aggressive behavior.2,10 Unneces-sary overtreatment of a benign lesion shouldbe avoided for obvious reasons: micrographic

surgery can be cost-prohibitive and a wide-localexcision has potential for significant cosmeticdisfigurement, given the typical location of theselesions (i.e. neck or upper trunk).

Fortunately, the two entities can be distin-guished by testing for the collagen type Ialpha 1-platelet-derived growth factor beta(COL1A1-PDGFB) fusion transcript, a byprod-uct of a t(17,22)(q22;q13) balanced translo-cation. This genetic anomaly is found in over90% of DFSP and leads to the upregulationof PDGFB, a tyrosine-kinase receptor.10 Eithermultiplex reverse transcription-polymerasechain reaction (RT-PCR) or dual color fusionfluorescence in-situ hybridization (FISH) canbe used to identify the fusion protein. Whileboth techniques can be used on formalin-fixedparaffin-embedded tissue, multiplex RT-PCRis more labor intensive and takes longer toperform.10,11 In addition, FISH is a more sensi-tive assay and is the preferred technique whentesting tissue that has been embedded for morethan 4 years.2

In summary, we describe a case which we feelis best classified as an example of plaque-likeCD34-positive dermal fibroma. Due to the lim-ited number of reported cases, we posit thatthe diagnostic spectrum of this entity is stillbeing established. We acknowledge that our casebears some overlap with FCTN and that the twoentities may coexist on a spectrum. Plaque-likeCD34-positive dermal fibroma should always beconsidered within the differential diagnosis ofCD34-positive dermal spindle cell neoplasms. Incases such as ours in which there is clinical andhistopathologic ambiguity or a lack of clinicalinformation, molecular testing may be usefulto differentiate plaque-like CD34-positive dermalfibroma from DFSP, as this diagnosis would resultin more aggressive treatment recommendations.

Fig 3. The neoplastic cells surround vessels ina vaguely storiform pattern.Fig 4. The spindled cells are concentricallyarranged around adnexal structures, which ishighlighted by CD34 immunostaining.Fig 5. The neoplastic cells show minimal cyto-logic atypia.Fig 6. There are scattered dilated vesselswithin the dermis.

References:1. Rodriguez-Jurado R, Palacios C,

Duran-McKinster C, et al. Medallion-likedermal dendrocyte hamartoma: a newclinically and histopathologically distinct

lesion. J Am Acad Dermatol 2004; 51:359.

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2. Kutzner H, Mentzel T, Palmedo G,et al. Plaque-like CD34-positive dermalfibroma ("medallion-like dermal den-drocyte hamartoma"): clinicopathologic,immunohistochemical, and molecularanalysis of 5 cases emphasizing its dis-tinction from superficial, plaque-likedermatofibrosarcoma protuberans. Am JSurg Pathol 2010; 34: 190.

3. Bagazgoitia L, Moreno C. Hypocellularmedallion-like dermal dendrocyte hamar-toma (plaque-like CD34-positive dermalfibroma). Dermatol Online J 2011; 17: 8.

4. Ducharme EE, Baribault KE, Husain S,Engler DE. Medallion-like dermal dendro-cyte hamartoma in a 36-year-old male. J AmAcad Dermatol 2008; 59: 169.

5. Marque M, Bessis D, Pedeutour F,Viseux V, Guillot B, Fraitag-SpinnerS. Medallion-like dermal dendrocytehamartoma: the main diagnostic pitfallis congenital atrophic dermatofibrosar-coma. Br J Dermatol 2009; 160: 190.

6. Martin JM, Jorda E, Monteagudo C, AlonsoV, Calduch L. Atrophic congenital lesionon the back. Arch Dermatol 2006; 142:921.

7. Restano L, Fanoni D, Colonna C, GelmettiC, Berti E. Medallion-like dermal dendro-cyte hamartoma: a case misdiagnosed asneurofibroma. Pediatr Dermatol 2010; 27:638.

8. Shah KN, Anderson E, Junkins-HopkinsJ, James WD. Medallion-like dermal

dendrocyte hamartoma. Pediatr Dermatol2007; 24: 632.

9. de Feraudy S, Fletcher CD. Fibroblasticconnective tissue nevus: a rare cutaneouslesion analyzed in a series of 25 cases. AmJ Surg Pathol 2012; 36: 1509.

10. Llombart B, Serra-Guillen C, MonteagudoC, Lopez Guerrero JA, Sanmartin O. Der-matofibrosarcoma protuberans: a compre-hensive review and update on diagnosisand management. Semin Diagn Pathol2013; 30: 13.

11. Walluks K, Chen Y, Woelfel C, et al. Molec-ular and clinicopathological analysis ofdermatofibrosarcoma protuberans. PatholRes Pract 2013; 209: 30.

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