Vol.34 No.3 Case report 207 Atypical with an Interstitial Granulomatous Pattern; A Difficult Case in Making Diagnosis Chanida Ungaksornpairote MD, Punkae Mahaisawariya MD. ABSTRACT: UNGAKSORNPAIROTE C, MAHAISAWARIYA P. ATYPICAL LICHEN MYXEDEMATOSUS WITH AN INTERSTITIAL GRANULOMATOUS PATTERN; A DIFFICULT CASE IN MAKING DIAGNOSIS. THAI J DERMATOL 2018; 34: 207216. DEPARTMENT OF DERMATOLOGY, FACULTY OF MEDICINE SIRIRAJ HOSPITAL, MAHIDOL UNIVERSITY, BANGKOK, THAILAND. Lichen myxedematosus (LM) is characterized by multiple discrete papules with shiny surface and area of induration caused by mucin deposition. There are 3 subtypes including the generalized papular and sclerodermoid form or scleromyxedema, the localized papular form, and the atypical or intermediate form. Histological characteristics can be classical mucin deposition or rare interstitial variant. The authors report an atypical case of LM with an interstitial granuloma histologic pattern which was rare and difficult to make a diagnosis. Key words: Atypical lichen myxedematosus, scleromyxedema, interstitial granulomatous

From: Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand Corresponding author : Chanida Ungaksornpairote MD., email : [email protected] 208 Ungaksornpairote C et al Thai J Dermatol, JulySeptember 2018

บทคัดยอ: ชนิดา อึ้งอักษรไพโรจน พรรณแข มไหสวริยะ โรคไลเคนมิกซิดีมาโตซุส ชนิดไมปกติ (ATYPICAL LICHEN MYXEDEMATOSUS) ที่มีลักษณะทางพยาธิวิทยาเปนแบบแกรนูโลมา ซึ่งยากตอการวินิจฉัย วารสารโรคผิวหนัง 2561; 34: 207216. ภาควิชาตจวิทยา คณะแพทยศาสตรศิริราชพยาบาล มหาวิทยาลัยมหิดล กรุงเทพมหานคร ประเทศไทย โรคไลเคนมิกซิดีมาโตซุส (Lichen myxedematosus) เปนโรคที่มีลักษณะทางคลินิกคือ มีตุมมันวาว หลายตุม อยูรวมกันเปนกลุม บนผิวหนังแข็ง สาเหตุเกิดจากการสะสมของสารมิวซิน ภายใตผิวหนังบริเวณนั้น โดยโรคนี้สามารถแบงออกไดเปน 3 ชนิด คือ แบบกระจายทั่วไป หรือ สเคลอโรมิกซิดีมา (scleromyxedema), แบบเฉพาะที่ และแบบไมปกติ ลักษณะทางพยาธิวิทยาที่พบปกติทั่วไปคือ มีสารมิวซิน สะสมภายในชั้นผิวหนังแท และนอยมากที่จะพบลักษณะทางพยาธิวิทยาแบบแกรนูโลมา คณะผูรายงานพบวา ผูปวยรายนี้มีโรคไลเคนมิกซิดีมาโตซุส ชนิดไมปกติ รวมกับมีลักษณะทางพยาธิวิทยาเปนแบบแกรนูโลมา ซึ่งพบ ไดนอยมาก และยากตอการวินิจฉัย คําสําคัญ: โรคไลเคนมิกซิดีมาโตซุสชนิดไมปกติ, สเคลอโรมิกซิดีมา, ลักษณะทางพยาธิวิทยาแบบแกรนูโลมา

Introduction (Figure1). 2,3 Scleromyxedema, also known as Lichen myxedematosus (LM) was formerly generalized and sclerodermoid LM, is a chronic referred as "generalized localized" myxedema. disease affecting the middleaged adults in their The disease is characterized by multiple discrete fifties to sixties with no significant gender papules with shiny surface and areas of predominance. 4 Cutaneous manifestations in induration caused by mucin deposition. The scleromyxedema are generalized sclerodermoid etiology of mucin accumulation in the dermis is eruption with multiple, firm, 1 to 3 mm flesh still unclear. One of the hypotheses suggests the colored papules, involving all parts of the body, role of circulating cytokines such as IL1, TNF including the face. The disease is often alpha and TGFbeta, and their ability to accompanied by . stimulate glycosaminoglycan synthesis and Extracutaneous manifestations such as fibroblast proliferation in the skin. 1 Rongioletti neurologic dysfunction, arthralgia, cardiac divided LM into 3 subtypes, which are the abnormalities, myositis, esophageal dysfunction generalized papular and sclerodermoid form or may be present. 4 In the localized form of LM, scleromyxedema, the localized papular form, sclerotic features, systemic involvement, and and the atypical or intermediate form monoclonal gammopathy are absent. This form Vol.34 No.3 Ungaksornpairote C et al 209 is also divided into 4 subtypes. 2,3 Firstly, a Additionally, the atypical form of LM lies in discrete papular form is characterized by a between scleromyxedema and the localized chronic, symmetrical eruption of small papules, form, thereby making it difficult to diagnosis. involving the limbs and trunk. Secondly, in acral Moreover, it can be categorized into 3 subtypes; persistent papular , the lesions are (1) scleromyxedema without monoclonal localized on the dorsum of the hands and gammopathy, (2) localized forms with extensor surface of the distal forearms. Thirdly, monoclonal gammopathy and/or systemic cutaneous mucinosis of infancy occurs in infants symptoms, and (3) not welldelineated cases. 2,3 with opalescent papules located on the upper Several cases were reported with different arms and the trunk. Lastly, in a pure nodular systemic involvement such as neurologic form, the lesions present with nodules on the dysfunction, cardiac or hematologic trunk and extremities without papules. abnormalities. 511

Figure 1. Types of Lichen myxedematosus

Classic histological findings in proliferation of irregularly arranged fibroblasts. 12 scleromyxedema comprised of a characteristic In localized form, mucin accumulates in the triad, including a diffuse deposit of mucin in the dermis but fibroblast proliferation is variable. 3 An upper and mid reticular dermis, associated with interstitial granuloma annulare like pattern has increased collagen deposition and marked been reported in several patients with 210 Ungaksornpairote C et al Thai J Dermatol, JulySeptember 2018 generalized form of scleromyxedema or Hereby, the authors present the case of an localized LM. 1320 atypical form of LM with the interstitial granulomatous histologic presentation.

Figure 2. Diagram showing disease progression and management

Case report flexion contracture of the fingers was observed A 75yearold woman presented with an on both sides. No other systemic symptoms eightmonth history of bilateral multiple were shown. Eventually, the patient decided to erythematous nodules on both hands. These come to Siriraj hospital. The timeline was shown lesions were painless and not itchy. in figure 2 . The patient went to a private hospital and On the physical examination, illdefined, was diagnosed with allergic contact dermatitis. indurated plaques with multiple waxy, skin She was, in turn, prescribed with a high potency colored flattop papules on top were observed topical corticosteroid. The lesions did not at neck, upper back, chest, and both upper arms respond to the topical treatment. A skin biopsy (Figure 3 ). Both hands showed symmetrical, was then done at a nodule on the right palm. multiple erythematous papules and nodules Nevertheless, the diagnosis was still inconclusive. mainly on the palmar sites. The surrounding skin Seven months later, she developed more showed like induration with flexion multiple skincolored nodules on both upper deformities and sclerodactyly ( Figure 4 ). Other arms, neck, upper back and chest. Also, both physical examinations were unremarkable. hands were swollen and tender. In addition,

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Figure 5. Histological finding from right palm; A, increased dermal mucin in the upper reticular dermis; B, superficial perivascular lymphocytic infiltrate and interstitial infiltrate of histiocytes (hematoxylineosin stain; A x 4, B x 40 original magnification).

Figure 3. Illdefined, indurated plaques with multiple waxy, skincolored flattop papules on A, B; both upper arms, and D; upper chest, C; magnified view of A.

Figure 6. Histological finding from right upper arm; Figure 4. Both hands showed sclerodermalike A, Focal aggregation of histiocytes in upper dermis induration with multiple erythematous papules and “Granuloma annulare like” pattern in upper nodules on top; A, dorsum; B, palmar. Sclerodactyly dermis; B, diffuse infiltration of histiocytes and mucin was presented (arrow). deposition throughout the whole thickness of dermis; C, positive mucin in Alcian blue pH 2.5; D, the mononuclear cell marked with CD 163 (hematoxylineosin stain; A, C and D x 4, B x 40 original magnification).

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The skin biopsy from the nodule at the right these cells stained positive for CD 163, factor palm which was done from another hospital was XIIIa and negative to AE1/AE2 and CD1a. reinspected. The section showed superficial Laboratory analysis was sent to screen perivascular lymphocytic infiltrate and interstitial systemic involvement and showed normal infiltrate of mononuclear cells in the dermis and complete blood count, liver function test and subcutaneous fat septum ( Figure 5 ). There was thyroid function test. Serum protein increased dermal mucin in the upper reticular electrophoresis, immunofixation electrophoresis dermis. The histopathological findings suggested and immunoglobulin free light chain assays the interstitial granuloma annulare. Given the could not detect any monoclonal gammopathy. clinical history of multiple shiny, skincolored The patient was diagnosed as an atypical papules and nodules on both arms and hands, form of LM with the interstitial granulomatous we suspected it was scleromyxedema. histologic variant. Since the patient was suffered Therefore, skin biopsy was repeated at the from sclerodactyly, we decided to give her oral papule on the right upper arm and chloroquine 250 mg per day and methotrexate immunohistochemistry for Alcian blue pH 2.5, 7.5 mg weekly, together with the rehabilitation CD163, AE1/AE3, CD1a and factor XIIIa was used for sclerodactyly and routine clinical follow ups to confirm the diagnosis. The immunostaining for the further systemic symptom. demonstrated that the mononuclear cells Discussion stained positive for CD 163 and factor XIIIa, but The authors hereby present the case of negative to AE1/AE2 and CD1a. The upper atypical LM type 4 (not welldelineated cases). reticular dermis was highlighted with Alcian blue She firstly developed with discrete papular pH 2.5. These stainings suggested histiocytic lesions on both palms. This presentation differentiation of the mononuclear cells and distinguished from acral persistent popular were compatible with granuloma annulare. The mucinosis form of LM, which localized lesion section from the skin biopsy at the papule on appeared at the dorsum of the hands and the right upper arm, which was 5 months after extensor surface of the distal forearms. Later, the first skin biopsy, revealed similar in pattern multiple papules and nodules at the trunk, both and staining (Figure 6). Dermal mucin was upper arms and palms appeared altogether with increased and stained positive with Alcian blue limited lichenoid sclerodermoid plaques on the pH 2.5. There was a diffused infiltration of upper part of the body and sclerodactyly mononuclear cells throughout the entire dermis, without monoclonal gammopathy. The clinical 214 Ungaksornpairote C et al Thai J Dermatol, JulySeptember 2018 findings of sclerodactyly and sclerodermoid who lacks monoclonal gammopathy. Since the changes of both hands can be seen in both time to diagnosis is 8 months for this patient limited form and diffused form of scleroderma. that was shorter than the other reported cases, However, the presence of a multiple waxy further systemic involvement and monoclonal nodulopapular eruption on the trunk, upper gammopathy need to be followed up. arms and palms are almost never involved in There is no specific guideline for the scleroderma. 21 The patient has no facial treatment of scleromyxedema. Rather, multiple involvement. The skin hardening was limited on modalities such as intravenous immunoglobulin, the nodulopapular area. Moreover, no calcinosis corticosteroids, chemotherapeutic agents, cutis, esophageal dysmotility, nor telangiectasia thalidomide, chloroquine, radiotherapy, and were found in our patient. autologous stem cell transplantation were The histological finding of the interstitial reported with variable outcomes. 4 For localized granulomatous pattern makes the disease more LM, the clinical course is usually spontaneous difficult to diagnose. The diagnosis of granuloma resolution. 2 Due to the limited data on atypical annulare would be without a doubt if the scleromyxedema, the prognosis is unpredictable. patient presented with only skincolored Therefore, further clinical follow up is necessary. papules. However, the clinical findings of Conclusion sclerodactyly and sclerodermoid changes of An unusual presentation of scleromyxedema both hands are unlikely to occur in granuloma can be presented with an unusual histological annulare. In contrast, the interstitial finding, as in the present case. The diagnosis is granulomatous pattern has been reported in considered difficult. Clinical correlation is an several patients with generalized form of important key to diagnosis this distinctive scleromyxedema or localized LM. 1320 Most of variation. Due to the unknown prognosis for the cases were accompanied by sclerodactyly atypical LM, the main treatment is to follow up and sclerodermoid skin manifestation, which was for further systemic involvement. similar to our patient. All the report cases Acknowledgement showed at least a monoclonal gammopathy. It The authors would like to express our sincere has been suggested that granulomatous gratitude toward Dr. Sumanas Bunyaratavej for inflammation is a reactive response to the sharing his interesting case and valuable support. monoclonal gammopathy. 15 However, this Potential conflicts of interest hypothesis could not be explained in our patient None. Vol.34 No.3 Ungaksornpairote C et al 215

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