A medal-worthy diagnosis: Medallion-like dermal dendrocyte hamartoma

By Warren R. Heymann, MD, FAAD
Aug. 30, 2023
Vol. 5, No. 34

A personal joy of dermatology is rendering a diagnosis in a lesion or rash that I have only read about but never previously encountered in practice. Beyond being intellectually satisfying, having a precise diagnosis is reassuring, as it allows an understanding of expectations, whether or not we grasp the underlying pathophysiology of the disorder. During a routine physical examination of a 61-year-old man, I noticed a suprasternal lesion; the patient confirmed that it was asymptomatic, present “for the longest time,” has not changed, and was never traumatized or treated. The location and morphology (round, atrophic, red-brown, with telangiectasia) are compatible with the diagnosis of a medallion-like dermal dendrocyte hamartoma (MLDDH, see attached image). This commentary delves into this unusual lesion. (Please note that the diagnosis of MLDDH in this patient is presumptive — a confirmatory biopsy was not performed as the lesion had been stable for decades.)

In 2004, the name MLDDH was proposed by Rodríguez-Jurado et al in reporting 3 female patients (ages 7, 10, and 11 years) with similar congenital lesions presenting on the supraclavicular region, presternal area, and neck, respectively. Histologically, all 3 patients showed a fusiform-cell proliferation. Immunohistochemistry was positive for CD34, factor XIIIa, and fascin. Electron microscopy showed typical features of dermal dendrocytes. Aside from naming the lesion, the authors appropriately suggested that more specific markers would be necessary to comprehend the nature of these lesions. (1)

In attempting to understand these lesions, some basic definitions are in order. According to Ducharme et al, dermal dendrocytes (dermal dendritic cells; DDCs) are bone marrow–derived, mesenchymal cells with a spindle cell or dendritic morphology. Two subtypes of dermal dendrocytes have been identified based on their immunohistochemical staining — factor XIIIa and CD34. Factor XIIIa (fibrin stabilizing factor) is a cytoplasmic transglutaminase involved in the blood clotting cascade serving as a marker of hematopoietic differentiation. CD34 (human progenitor cell antigen) is a cell surface glycoprotein marker of vascular endothelial cells and lymphopoietic progenitor cells whose precise function is unknown. Type 1 dermal dendrocytes are factor XIIIa+ and CD34–; they may be seen with inflammatory disorders (atopic dermatitis, psoriasis, late-stage morphea), and neoplastic processes (fibrous papule, atypical fibroxanthoma, early stage Kaposi sarcoma). Type II dermal dendrocytes are CD34+ and factor XIIIa–; these are increased in dermatofibrosarcoma protuberans (DFSP), spindle cell lipomas, and Kaposi sarcoma. The relationship between the two types of dermal dendrocytes remains to be elucidated. (2)

As anticipated by Rodríguez-Jurado et al, further studies have added to our knowledge. Shah et al reported a case of MLDDH in a 19-year-old woman. Histologically this case was positive for CD34 but negative for factor XIIIa. (3) Kutzner et al proposed expanding the concept of MLDDH to include plaque-like lesions, that may be observed on the extremities, suggesting the term plaque-like CD34-postive dermal fibroma. (4) Recent literature often uses the nomenclature plaque-like CD34-positive dermal fibroma/MLDDH suggesting a spectrum of disease. Some of these cases may be acquired, such as the case of a 9-year-old girl whose neck lesion appeared 6 months before presentation. (3) While all of these cases exhibit a similar immunohistochemical profile and may be related (5), in my opinion it is debatable if they should be considered one and the same. They are clinically distinct (MLDDH — congenital, atrophic, distributed mostly on the neck and trunk; plaque-like CD34-postive dermal fibroma — acquired, raised, distributed mostly on the extremities). Fortunately, both variants are benign. From my perspective, MLDDH is clinically recognizable. I cannot imagine even the most astute clinician rendering this diagnosis for a nondescript skin-colored dermal nodule or plaque.

An important clinical consideration is differentiating MLDDH from other similar disorders, such as aplasia cutis, atrophoderma (morphea), anetoderma, and neurofibroma. (6) There may be overlapping features with a fibroblastic connective tissue nevus (FCTN). According to Horikawa et al: “Fibroblastic connective tissue nevus was first described in 2012 as a new type of CD34 -positive skin lesion presenting as a solitary painless plaque-like or nodular lesion. It usually appears in children but sometimes in adults. Pathologically, it arises in the reticular dermis with entrapping appendages and often infiltrates into the superficial subcutis. Epidermal papillomatosis and dermal ectopic adipose tissue are sometimes observed (70% and 60.6%, respectively). Staining for CD34 in FCTN is typically patchy and weak, whereas that in MLDDH is diffuse and strong.” (7)

The most crucial differential diagnosis is a congenital atrophic dermatofibrosarcoma protuberans (DFSP) which share clinical, histopathological and immunohistochemical features. Both are positive for CD34, but DFSP is routinely negative for factor XIIIa. In cases showing ambiguous immunohistochemical results, the fluorescence in situ hybridization (FISH) analysis using two-color probes for COL1A1 and PDGFB genes is a useful tool to differentiate DFSP from MLDDH, because DFSP displays the gene translocation t(17;22)(q22;q13) and chimeric COL1A1-PDGFB mRNA expression. (8) Marque et al emphasize that these molecular studies are vital in securing the correct diagnosis so that MLDDH patients avoid unnecessary mutilating surgery. (9) This differential is critical in patients with adenosine deaminase-deficient severe combined immunodeficiency as these patients are at high risk of DFSP tumors resembling MLDDH. (10)

Point to Remember: The clinically distinctive medallion-like dermal dendrocyte hamartoma is a benign lesion that must be differentiated from congenital atrophic dermatofibrosarcoma protuberans, especially in patients with adenosine deaminase-deficient severe combined immunodeficiency. Much remains to be learned about this enigmatic lesion and its relationship to other CD34-positive lesions such as the plaque-like CD34-positive dermal fibroma and the fibroblastic connective tissue nevus.

Our expert’s viewpoint

Jacqueline Junkins-Hopkins, MD, FAAD
Associate, Dermatopathology and Dermatology
Geisinger Medical Center, Danville, Pennsylvania

I agree with Dr. Heymann that medallion-like dermal dendrocytic hamartoma (MLDDH) is clinically recognizable, once one is familiar with the characteristic sharply circumscribed brownish red patch with atrophy that exposes the underlying vessels. (1) The medallion component of the name highlights this distinct clinical morphology, so one might ask, is the proposed name change (4) to plaque-like CD34 positive dermal fibroma (PDH) warranted?

But why should the name matter? As proposed by the soliloquy in Shakespeare’s Romeo and Juliet, “What’s in a name? That which we call a rose by any other name would smell just as sweet.” Does changing the name negate the ability to recognize this tumor? The proposed new name scraps the medallion descriptive and redirects us to a morphologically different clinical lesion, since plaques are typically raised, or at least thickened lesions, while the initially and subsequently reported MLDDH were atrophic and depressed. (2,3,9) The single congenital lesion in the series of Kutzner et al. (4) does have the typical atrophic medallion-like appearance, but the adult onset acral plaques do not. The acral site should not negate a diagnosis of MLDDH, as atrophic childhood MLDDH have been reported on the thigh and hand (9), but promoting the lesion as a fibroma expands the definition to include firm protuberant nodular lesions, such as that reported by Stuart et al. (5), which I do not think clinically represents the same entity.

The histopathologic features have also been expanded. The typical childhood MLDDH shows epidermal atrophy overlying a fusiform cell proliferation with fragmented and diminished elastic fibers that extends from the reticular or papillary dermis (at least in the image of the original paper by Rodriguez [1]) into the subcutaneous adipose tissue. (1,4) The congenital onset case in the Kutzner et al series with classic MLDDH morphology similarly extends into the subcutis. However, in contrast, the adult-onset lesions spare the subcutis and papillary dermis, presenting as plaque-like replacement of the upper two thirds of the dermis with overlying rete hyperplasia and vertical arrangement of fusiform cells in the upper dermis, beneath which are horizontally arranged fusiform cells with underlying compression of elastic fibers. Given the clinical and histopathologic disparity between the adult-onset lesions and the childhood onset/congenital lesions, these appear to represent two possibly related but separate entities.

The new name was also proposed to address the inaccuracies associated with the initial name. I have engaged in such behavior in proposing the term neutrophilic dermatosis of the dorsal hands to describe what had previously been called pustular vasculitis of the hands (11), to de-emphasize the vasculitis component and to stress the neutrophilic dermatosis association. It is now considered under the umbrella of Sweet syndrome. Likewise, because MLDDH does not always express Factor 13a, Kutzner et al assumed the fusiform cell to be a fibroblast, implying a reactive etiology; and thus, replaced the dermal dendrocyte and hamartoma with fibroma. [2] But is the fusiform CD34 expressing cell that characterizes MLDDH truly a fibroblast? Rodriguez et al concluded that the ultrastructural features “ruled out the possibility of a fibroblastic nature of the lesion.” (1) The terminology for these CD34 positive fusiform/spindled/dendritic cell is confusing, and this ambiguity is reflected in the literature. (12) As summarized by Dr. Heymann, these dermal fusiform “dendritic” cells have been classified according to CD34 vs Factor XIIIa expression. Some investigators have concluded that CD34+ dermal dendritic cells are different from dermal dendrocytes and fibroblasts, the latter of which are felt to not to express CD34. (13) Others have suggested that CD34+ fusiform cells and factor XIIIa dermal dendrocytes represent the same lineage cell with a variable phenotype according to location and/or local factors (14), or may represent uncommitted stem cells with the potential to differentiate towards fibroblasts or factor XIIIa dermal dendrocytes. The telocyte, a “new” kid on the block, is a CD34+dendritic interstitial cell (present in the dermis and in most organs) that interacts with a variety of stromal cells including fibroblasts, and plays a role in tissue renewal, mechanical support, and immune modulation, as well as in neoplastic and non-neoplastic cutaneous disorders. (14,15,16,17) The telocyte, while similar to the fibroblast on light microscopy, is ultrastructurally distinct from fibroblasts. (18) Could this be the cell of origin in MLDDH/PDH? Perhaps applying a broader name to the entity such as telocytoma, with two subtypes, MLDDH and PDH, might be an alternative approach. Lump, and then split.

But back to the question, what is in a name? If we settle on medallion-like dermal dendrocyte hamartoma and accept the original clinical description, the name directs us toward the option of a conservative management approach, as taken by Dr. Heymann. Regardless of the name, or fibroblast/dendrocyte/telocyte nature of the lesion, it is important to recognize that the lesion is benign. But since these lesions may microscopically mimic dermatofibrosarcoma protuberans, once a biopsy specimen from either clinical morphology is obtained, the specimen should be sent for molecular analysis. Fortunately, Kutzner et al have documented that fluorescence in situ hybridization is a reliable means to distinguish these lesions from DFSP. (4)

So is a name change warranted? My opinion is a cautious “yes,” but which name? Should the term reflect a unifying concept that includes a broad spectrum of clinical-pathologic entities, such as that proposed by Kutzner et al.? Or should it maintain the concept of two distinct entities, that being the originally described atrophic lesion arising in kids and the adult-onset plaque or nodular lesion? One approach could straddle both concepts. Aspects of both names, MLDDH and PDF, could be incorporated into a unifying term, such as “Medallion-like (as a nod to the original description and to emphasize the classic clinically recognizable presentation) CD34+ dermal dendritic cell lesion” (because it is not clear whether this represents a neoplasm or a hamartoma). Keeping the medallion descriptive eliminates the protruding nodules, but I suspect such lesions may represent a different entity. Alternatively, akin to the spectrum of CD30 positive lymphoproliferative disorders, where similar histopathologic findings are subcategorized into lymphomatoid papulosis or anaplastic large cell lymphoma based on the clinical morphology (19), I propose calling these “CD34 positive dermal dendritic cell lesions,” with “medallion-like” and “plaque-like” subtypes, depending on the clinical presentation. Further investigation of additional cases can help determine whether or how to further split or lump this unique and enigmatic lesion.

1. Rodríguez-Jurado R, Palacios C, Durán-McKinster C, Mercadillo P, Orozco-Covarrubias L, Saez-de-Ocariz Mdel M, Ruiz-Maldonado R. Medallion-like dermal dendrocyte hamartoma: a new clinically and histopathologically distinct lesion. J Am Acad Dermatol. 2004 Sep;51(3):359-63. doi: 10.1016/j.jaad.2003.11.070. PMID: 15337977.

2. Ducharme EE, Baribault KE, Husain S, Engler DE. Medallion-like dermal dendrocyte hamartoma in a 36-year-old male. J Am Acad Dermatol. 2008 Jul;59(1):169-72. doi: 10.1016/j.jaad.2008.03.003. PMID: 18571607.

3. Shah KN, Anderson E, Junkins-Hopkins J, James WD. Medallion-like dermal dendrocyte hamartoma. Pediatr Dermatol. 2007 Nov-Dec;24(6):632-6. doi: 10.1111/j.1525-1470.2007.00552.x. PMID: 18035985.

4. Kutzner H, Mentzel T, Palmedo G, Hantschke M, Rütten A, Paredes BE, Schärer L, Guillen CS, Requena L. Plaque-like CD34-positive dermal fibroma ("medallion-like dermal dendrocyte hamartoma"): clinicopathologic, immunohistochemical, and molecular analysis of 5 cases emphasizing its distinction from superficial, plaque-like dermatofibrosarcoma protuberans. Am J Surg Pathol. 2010 Feb;34(2):190-201. doi: 10.1097/PAS.0b013e3181c7cf11. PMID: 20061935.

5. Stuart LN, Hiatt KM, Zaki Z, Gardner JM, Shalin SC. Plaque-like CD34-positive dermal fibroma/medallion-like dermal dendrocyte hamartoma: an unusual spindle cell neoplasm. J Cutan Pathol. 2014 Aug;41(8):625-9. doi: 10.1111/cup.12375. Erratum in: J Cutan Pathol. 2014 Nov;41(11):895. PMID: 25065391.

6. Restano L, Fanoni D, Colonna C, Gelmetti C, Berti E. Medallion-like dermal dendrocyte hamartoma: a case misdiagnosed as neurofibroma. Pediatr Dermatol. 2010 Nov-Dec;27(6):638-42. doi: 10.1111/j.1525-1470.2010.01324.x. Epub 2010 Nov 24. PMID: 21092057.

7. Horikawa H, Sato T, Gomi H, Yamazaki K, Ishida Y, Yuzaki I, Fukuzumi S. Medallion-like dermal dendrocyte hamartoma: A rare congenital CD34-positive dermal lesion clinically and pathologically overlapping with fibroblastic connective tissue nevus. Pediatr Dermatol. 2019 May;36(3):397-399. doi: 10.1111/pde.13766. Epub 2019 Feb 27. PMID: 30811625.

8. Cheon M, Jung KE, Kim HS, Lee JY, Kim HO, Park CK, Park YM. Medallion-like dermal dendrocyte hamartoma: differential diagnosis with congenital atrophic dermatofibrosarcoma protuberans. Ann Dermatol. 2013 Aug;25(3):382-4. doi: 10.5021/ad.2013.25.3.382. Epub 2013 Aug 13. PMID: 24003290; PMCID: PMC3756212.

9. Marque M, Bessis D, Pedeutour F, Viseux V, Guillot B, Fraitag-Spinner S. Medallion-like dermal dendrocyte hamartoma: the main diagnostic pitfall is congenital atrophic dermatofibrosarcoma. Br J Dermatol. 2009 Jan;160(1):190-3. doi: 10.1111/j.1365-2133.2008.08896.x. Epub 2008 Oct 22. PMID: 19016705.

10. Cowen EW, Pichard DC, Garabedian E, Miettinen M. Medallion-Like Dermal Dendrocytic Hamartoma, Dermatofibrosarcoma Protuberans, and Adenosine Deaminase-Deficient Severe Combined Immunodeficiency. Pediatr Dermatol. 2016 May;33(3):359-60. doi: 10.1111/pde.12847. PMID: 27176810; PMCID: PMC4868401.

11. Galaria NA, Junkins-Hopkins JM, Kligman D, James WD. Neutrophilic dermatosis of the dorsal hands: pustular vasculitis revisited. J Am Acad Dermatol. 2000 Nov;43(5 Pt 1):870-4. doi: 10.1067/mjd.2000.109286. PMID: 11050599.Diaz-Flores Histol Histopathol (2014) 29: 831-870 DOI: 10.14670/HH-29.831.

12. Díaz-Flores L, Gutiérrez R, García MP, Sáez FJ, Díaz-Flores L Jr, Valladares F, Madrid JF. CD34+ stromal cells/fibroblasts/fibrocytes/telocytes as a tissue reserve and a principal source of mesenchymal cells. Location, morphology, function and role in pathology. Histol Histopathol. 2014 Jul;29(7):831-70. doi: 10.14670/HH-29.831. Epub 2014 Feb 3. PMID: 24488810.

13. Narvaez D, Kanitakis J, Faure M, Claudy A. Immunohistochemical study of CD34-positive dendritic cells of human dermis. Am J Dermatopathol. 1996 Jun;18(3):283-8. doi: 10.1097/00000372-199606000-00008. PMID: 8806963.

14. Sueki H, Whitaker D, Buchsbaum M, Murphy GF. Novel interactions between dermal dendrocytes and mast cells in human skin. Implications for hemostasis and matrix repair. Lab Invest. 1993 Aug;69(2):160-72. PMID: 8102416.

15. Ahmed AM, Hussein MR. Telocytes in Cutaneous Biology: A Reappraisal. Actas Dermosifiliogr. 2022 Nov 1:S0001-7310(22)00908-5. English, Spanish. doi: 10.1016/j.ad.2022.08.023. Epub ahead of print. PMID: 36332689.

16. Wei XJ, Chen TQ, Yang XJ. Telocytes in Fibrosis Diseases: From Current Findings to Future Clinical Perspectives. Cell Transplant. 2022 Jan-Dec;31:9636897221105252. doi: 10.1177/09636897221105252. PMID: 35748420; PMCID: PMC9235300.

17. Díaz-Flores L, Gutiérrez R, García MP, González-Gómez M, Rodríguez-Rodriguez R, Hernández-León N, Díaz-Flores L Jr, Carrasco JL. Cd34+ Stromal Cells/Telocytes in Normal and Pathological Skin. Int J Mol Sci. 2021 Jul 8;22(14):7342. doi: 10.3390/ijms22147342. PMID: 34298962; PMCID: PMC8307573.

18. Kang Y, Zhu Z, Zheng Y, Wan W, Manole CG, Zhang Q. Skin telocytes versus fibroblasts: two distinct dermal cell populations. J Cell Mol Med. 2015 Nov;19(11):2530-9. doi: 10.1111/jcmm.12671. Epub 2015 Sep 28. PMID: 26414534; PMCID: PMC4627559.

19. Kempf W, Kerl K, Mitteldorf C. Cutaneous CD30-positive T-cell lymphoproliferative disorders-clinical and histopathologic features, differential diagnosis, and treatment. Semin Cutan Med Surg. 2018 Mar;37(1):24-29. PMID: 29719017.

20. Image published with permission from Dr. Heymann.

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