10.5826/dpc.1304a241
text/xml
2160-9381
3421
en
Ting-Ting Yang
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
myelodysplastic syndrome
M2 Polarization May Contribute to Formation of Granulomatous Dermatitis in Progression of Myelodysplastic Syndrome to Acute Myeloid Leukemia 
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2023-10-31
2023-04-11
2023-10-31
2024-01-16
e2023241
Dermatol Pract Concept
Ting-Ting Yang
2023/10/31
10.5826/dpc.1304a241
e2023241
Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2160-9381
myelodysplastic syndrome
en
e2023241
Zhang G, Yang L, Han Y, Niu H, Yan L, Shao Z, et al. Abnormal Macrophage Polarization in Patients with Myelodysplastic Syndrome. Mediators Inflamm. 2021;2021:9913382.
M2 Polarization May Contribute to Formation of Granulomatous Dermatitis in Progression of Myelodysplastic Syndrome to Acute Myeloid Leukemia 
https://dpcj.org/index.php/dpc/article/download/3421/2366
        M2 Polarization May Contribute to Formation
        of Granulomatous Dermatitis in Progression
           of Myelodysplastic Syndrome to Acute
                     Myeloid Leukemia
    Wei-Cheng Fang1,5, Jeng-Shiun Du2,4, Yue-Chiu Su3,4, Li-Wen Chiu1,4, Ting-Ting Yang1,4


1 Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2 Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
3 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
4 Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5 Department of Dermatology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan



Key words: granulomatous dermatitis, myelodysplastic syndrome, acute myeloid leukemia, M2 macrophage
Citation: Fang WC, Du JS, Su YC, Chiu LW, Yang TT. M2 Polarization May Contribute To Formation Of Granulomatous Dermatitis
In Progression Of Myelodysplastic Syndrome To Acute Myeloid Leukemia. Dermatol Pract Concept. 2023;13(4):e2023241.
DOI: https://doi.org/10.5826/dpc.1304a241
Accepted: April 30, 2023; Published: October 2023
Copyright: ©2023 Fang et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Ting-Ting Yang, MD, 100 Shih-Chuan 1st Rd, Department of Dermatology, Kaohsiung Medical University
Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Tel: 886-7-3208223 E-mail: tingalingyang@gmail.com




Introduction                                                             abdomen, and anterior aspect of limbs for 1 week (­ Figure 1,
                                                                         A and C). Associated symptoms included fever and malaise.
Myelodysplastic syndromes (MDS) are a group of clonal he-                Laboratory tests revealed progressing pancytopenia with
matopoietic disorders which may convert into acute myeloid               increased blast cells. Gross examination of the skin biopsy
leukemia (AML). Cutaneous manifestations are uncom-                      specimen revealed black stone-like materials ­
                                                                                                                      (Figure 1B).
mon but can be the first clinical sign of disease progression.           ­According to the patient, he had survived a mining acci-
Herein, we report a MDS patient who abruptly developed                   dent 43 years ago, leaving multiple asymptomatic subcuta-
florid foreign body granulomas when progressing to AML.                  neous blue-gray papules over the face, trunk, and anterior
                                                                         aspect of extremities. Histopathological examination re-
Case Presentation                                                        vealed foreign body granulomas with black substances in
                                                                         the deep dermis and subcutis infiltrated with multinucleated
A 73-year-old Asian male with MDS-excess blasts-2                        giant cells, histiocytes and lymphocytes (Figure 2A). No
(MDS-EB-2) presented with multiple scattered, painful er-                blasts or neoplastic cells were noted. Immunohistochem-
ythematous to violaceous nodules over the face, chest,                   ical staining was negative for CD34, lysozyme, CD117,



Research Letter | Dermatol Pract Concept. 2023;13(4):e2023241                                                                       1
        Figure 1. Clinical images of foreign bodies and treatment response of the patient. (A) Multiple scattered, erythematous,
        violaceous, and painful nodules over face, chest, abdomen, and anterior aspect of 4 limbs. (B) Black stone-like foreign bod-
        ies. (C) Cutaneous presentation before systemic corticosteroid treatment. (D) Lesions resolved after systemic corticosteroid
        treatment.




and myeloperoxidase (Figure 2B). The infiltrated cells were             progression to AML [1-3]. We present a case of florid foreign
composed of CD68-positive cells (Figure 2C) and numerous                body granulomatous reaction associated with MDS progres-
CD163-positive cells (Figure 2D). Tissue cultures were all              sion to AML. M2 macrophages play an important role in
negative. Intravenous methylprednisolone 80 mg/day was                  granuloma formation [4], which may be the link between
administered and the erythematous granulomatous nodules                 the two phenomena. Immunohistochemical staining of the
resolved within 1 week, reverting to its original blue grey ap-         foreign body granulomas showed infiltration of CD163+ M2
pearance (Figure 1D). Unfortunately, the patient progressed             macrophages with elevated CD163/CD68 ratio. As for MDS
into AML within 1 month and died shortly after.                         transformation to AML, recent reports have shown the im-
                                                                        portance of M2-like tumor-associated macrophages (TAMs)

Conclusions                                                             with elevated CD163/CD68 ratio [5]. The macrophages in
                                                                        the bone marrow of high risk MDS patients were shown to
Granulomatous dermatitis, including cutaneous sarcoid-                  polarize to M2 and not to M1 macrophages leading to in-
osis, granuloma annulare and necrobiosis lipoidica have all             sufficient antitumor effect [6]. Therefore, we hypothesized
been reported to herald the onset of MDS or precede MDS                 that the increased M2 macrophage population in the present




2                                                                           Research Letter | Dermatol Pract Concept. 2023;13(4):e2023241
                           Figure 2. Histopathology and immunohistochemical staining of skin biopsy. (A)
                           Histopathological examination revealed retained foreign bodies in the deep der-
                           mis and subcutis infiltrated with multinucleated giant cells, histiocytes and lym-
                           phocytes (hematoxylin and eosin, original magnification ×20). (B) Cells in foreign
                           body granulomas showed negative for myeloperoxidase (immunohistochemistry
                           for myeloperoxidase, original magnification ×200). (C) Multiple scattered CD68+
                           macrophages in foreign body granuloma (immunohistochemistry for CD68, orig-
                           inal magnification ×200). (D) A large number of CD163+ macrophages in foreign
                           body granuloma (immunohistochemistry for CD163, original magnification ×200).




case was due to M2 polarization in the bone marrow. These              2. Balin SJ, Wetter DA, Kurtin PJ, Letendre L, Pittelkow MR. My-
M2 macrophages were then attracted by the foreign body in                   elodysplastic syndrome presenting as generalized granulomatous
                                                                            dermatitis. Arch Dermatol. 2011;147(3):331-5. DOI: 10.1001
the skin, thus leading to acute foreign body granulomatous
                                                                            /archdermatol.2011.39. PMID: 21422341.
reaction.
                                                                       3.   Cornejo KM, Lum CA, Izumi AK. A cutaneous interstitial granu-
   In summary, we present a case of a MDS patient with                      lomatous dermatitis-like eruption arising in myelodysplasia with
subsequent progression to AML associated with an abrupt                     leukemic progression. Am J Dermatopathol. 2013;35(2):e26-e29.
appearance of diffuse foreign body granulomas. Predomi-                     DOI: 10.1097/DAD.0b013e31826ff6a6. PMID: 23221468.
nant M2 macrophages in the foreign body granulomas may                 4.   Terai S, Ueda-Hayakawa I, Nguyen CTH, et al. Palisaded neu-
                                                                            trophilic and granulomatous dermatitis associated with systemic
correlate to M2 polarization in the bone marrow of high risk
                                                                            lupus erythematosus: possible involvement of CD163(+) M2 mac-
MDS or AML patients. Therefore, it is important to recog-
                                                                            rophages in two cases, and a review of published works. Lupus.
nize that the granulomatous dermatitis in MDS patients may                  2018;27(14):2220-2227. DOI: 10.1177/0961203318809892.
associate with disease progression and poor prognosis.                      PMID: 30376790.
                                                                       5.   Cencini E, Fabbri A, Sicuranza A, Gozzetti A, Bocchia M. The
                                                                            Role of Tumor-Associated Macrophages in Hematologic Ma-
References                                                                  lignancies. Cancers (Basel). 2021;13(14):3597. DOI: 10.3390
                                                                            /cancers13143597. PMID: 34298810. PMCID: PMC8304632.
 1. Vestey JP, Turner M, Biddlestone L, McLaren K, Goulden N,
                                                                       6.   Zhang G, Yang L, Han Y, et al. Abnormal Macrophage Polar-
    Hunter JA. Disseminated cutaneous granulomatous eruptions
                                                                            ization in Patients with Myelodysplastic Syndrome. Mediators
    associated with myelodysplastic syndrome and acute myeloid
                                                                            Inflamm. 2021;2021:9913382. DOI: 10.1155/2021/9913382.
    leukaemia. Clin Exp Dermatol. 1993;18(6):559-563. DOI:
                                                                            PMID: 34335093. PMCID: PMC8286189.
    10.1111/j.1365-2230.1993.tb01031.x. PMID: 8252798.




Research Letter | Dermatol Pract Concept. 2023;13(4):e2023241                                                                             3
