10.5826/dpc.1301a9
text/xml
2160-9381
2355
en
Angelo Valerio Marzano 
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
cutaneos involvement
Dermal Amyloid Deposits: A Possible Misleading Pathologic Finding
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2023-01-31
2022-01-30
2023-01-31
2023-02-27
e2023009
Dermatol Pract Concept
Angelo Valerio Marzano 
2023/01/31
10.5826/dpc.1301a9
e2023009
UOC Dermatologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico; Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy
2160-9381
cutaneos involvement
en
e2023009
Wu B, Pak DM, Smith KD, Shinohara MM. Utility of abdominal skin punch biopsy for detecting systemic amyloidosis. J Cutan Pathol. 2021;48(11):1342-1346. DOI: 10.1111/cup.14070. PMID: 34075607.
Dermal Amyloid Deposits: A Possible Misleading Pathologic Finding
https://dpcj.org/index.php/dpc/article/download/2355/1969
                     Dermal Amyloid Deposits: A Possible
                        Misleading Pathologic Finding
                 Serena Giacalone1,2, Carlo Alberto Maronese1,2, Giovanni Genovese1,2,
                              Marco Cusini1, Angelo Valerio Marzano1,2


1 UOC Dermatologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
2 Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy



Key words: amyloid deposits, drug eruption, systemic amyloidosis, cutaneous involvement
Citation: Giacalone S, Maronese CA, Genovese G, Cusini M, Marzano AV. Dermal Amyloid Deposits: A Possible Misleading Pathologic
Finding. Dermatol Pract Concept. 2023;13(1):e2023009. DOI: https://doi.org/10.5826/dpc.1301a9
Accepted: May 9, 2022; Published: January 2023
Copyright: ©2023 Giacalone 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: Serena Giacalone, MD, Unità Operativa di Dermatologia, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore
Policlinico, Via Pace 9, Milan, Italy. Telephone: +390255034718 Fax: +390255033562 E-mail: serenagiacalone92@gmail.com




Introduction                                                             localization and abundance of amyloid deposits. Generally,
                                                                         amyloid deposition affects dermal blood vessels, that easily
Amyloid is a highly organized fibrillar substance resistant to           rupture upon minimal trauma, with subsequent appearance
macrophage degradation. It can originate from more than                  of petechiae, purpura and ecchymoses, mostly located on
27 misfolded proteins. Extracellular amyloid deposition may              body folds. Profuse infiltration of amyloid within the dermis
result from several pathophysiological processes: abnormal               and the subcutis can manifest also as papules, plaques, nod-
protein production, excessive presence of normal proteins or             ules, bullae, and even scleroderma-like lesions. Amyloid infil-
senescence. Recently, reclassification of amyloidosis based              tration in or about sweat glands, sebaceous glands, and hair
on protein type led to the identification of subgroups with              follicles can result in anhidrosis and alopecia [2]. Curiously,
different etiology (acquired or inherited), clinical manifesta-          amyloid deposits have been demonstrated in all of the afore-
tions, and prognosis [1]. Some forms are localized while oth-            mentioned sites, also in clinically uninvolved skin [3]. Here,
ers involve multiple organs. Dermal amyloid deposits can be              we present a case of massive dermal amyloid deposit both in
detected in both cases. Cutaneous localized amyloidosis in-              involved and uninvolved skin that mislead clinical diagnosis.
cludes keratinic and nodular amyloidosis. In the first case the
macular and lichenoid lesions correspond to subtle deposits
                                                                         Case Presentation
limited to the upper dermis, in the second case plaque and
nodules are secondary to deep dermal and subcutis deposits.              A 53-year-old man presented with a pruritic, non-confluent,
    The spectrum of cutaneous involvement in systemic am-                maculopapular eruption of one month duration, consisting
yloidosis encompasses a wide variety of lesions that reflect             of discrete 5-10 mm lesions, symmetrically distributed on his




Research Letter | Dermatol Pract Concept. 2023;13(1):e2023009                                                                         1
trunk, arms and upper thighs (Figure 1). His medical history               Two additional punch biopsies were performed, on le-
was significant for multiple myeloma and systemic amyloid              sional and non-lesional areas, respectively. The former
light-chain (AL) amyloidosis with cardiac, gastric and bone            showed diffuse vacuolar change in the basal layer of the epi-
marrow involvement. He had been treated with allogenic                 dermis with scattered necrotic keratinocytes and a band-like
bone marrow transplantation followed by bortezomib, en-                superficial inflammatory infiltration. Amyloid deposits were
doxaban and dexamethasone without any adverse cutaneous                detected in both specimens. Finally, a diagnosis of lichenoid
reaction. The patient received pomalidomide ten days before            drug eruption in the setting of systemic AL amyloidosis with
the onset of the rash and the drug was promptly discon-                concomitant massive dermal amyloid deposits was made.
tinued. He complained of xerostomia and development of
hematomas after mild trauma. Histological examination re-
                                                                       Conclusions
vealed presence of multiple hyaline deposits in the superficial
dermis, with perivascular, peri-adnexal, and interstitial ar-          Globally, mucocutaneous lesions have been described in
rangement (Figure 2A). Congo-red staining positivity along             30% of all cases of systemic amyloidosis, and in up to 50%
with apple-green birefringence under polarized light was               those with AL type [4]. Although the dermatologist may
consistent with amyloid (Figure 2B). Immunohistochemical               have a crucial role in the prompt diagnosis of systemic am-
typing of amyloid revealed lambda light chain accumulation             yloidosis [5], massive presence of cutaneous amyloid, as in
(Figure 2C).                                                           our case, could mislead both the dermatologist and the pa-
    A course with prednisone 25 mg daily tapered over three            thologist involved in the diagnostic process, masking other
weeks quickly led to clinical resolution of the eruption.              concurrent disorders. Indeed, detection of amyloid deposits
However, 3 days following pomalidomide reintroduction,                 in normal-appearing skin has been widely demonstrated
sudden reappearance of the same monomorphous lesions                   in literature: in the past, several studies proposed to per-
was observed.                                                          form biopsy on uninvolved skin to confirm systemic cases




Figure 1. Non-confluent, maculopapular eruption of discrete 5-10 mm lesions on patient lower back (A), right arm (B) and right forearm (C).




Figure 2. Histopathology showing diffuse vacuolar change in the basal layer of the epidermis with scattered necrotic keratinocytes and a
band-like superficial inflammatory infiltration. (A) H&E x200 Notice dermal amyloid deposit (black arrows). (B) Congo red stain highlight-
ing dermal perivascular, peri-adnexal, and interstitial infiltration of amyloid. (C) Immunohistochemical typing of amyloid revealing lambda
light chain accumulation.



2                                                                           Research Letter | Dermatol Pract Concept. 2023;13(1):e2023009
of amyloidosis [3]. However, even if type of dermatological     2. Schreml S, Szeimies RM, Vogt T, Landthaler M, Schroeder J,
findings depends on amyloid localization, the exact amount         Babilas P. Cutaneous amyloidoses and systemic amyloidoses with
                                                                   cutaneous involvement. Eur J Dermatol. 2010;20(2):152-160.
of deposit capable to trigger clinical modification has not
                                                                   DOI: 10.1684/ejd.2010.0842. PMID: 20071301.
yet been identified. In systemic amiloidosis, the presence of
                                                                3. Rubinow A, Cohen AS. Skin involvement in generalized amy-
deposits in uninvolved sites enforces the idea that detection      loidosis. A study of clinically involved and uninvolved skin in
of amyloid in cutaneous lesions should not lead to hasty           50 patients with primary and secondary amyloidosis. Ann Intern
diagnostic conclusions. Although the possible cutaneous            Med. 1978;88(6):781-785. DOI: 10.7326/0003-4819-88-6-781.
manifestations of systemic amyloidosis are protean, clinical       PMID: 666134.
                                                                4. Flores-Bozo LR, Echevarría-Keel J, Domínguez-Cherit J,
confirmation bias should always be considered and avoided.
                                                                   Esquivel-Pedraza L, Méndez-Flores S. Mucocutaneous manifes-
                                                                   tations in systemic amyloidosis A retrospective analytical study
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Research Letter | Dermatol Pract Concept. 2023;13(1):e2023009                                                                    3
