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\begin{document}

\title{Leukemia Cutis presenting as Hyperpigmented patches. A rare presentation}



\author[1]{Nastaran Namazi}%
\author[1]{Zahra Asadi Kani}%
\author[2]{Ali  kaddah }%
\author[1]{Reem Diab}%
\affil[1]{Shahid Beheshti University of Medical Sciences}%
\affil[2]{Shaheed Beheshti University of Medical Sciences}%


\vspace{-1em}



  
  \date{June 12, 2024}


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\selectlanguage{english}
\begin{abstract}
Leukemia cutis is a cutaneous manifestation of leukemia. Herein, we
present a rare cutaneous manifestation of leukemia cutis in a patient
with myeloid leukemia m5, characterized by hyperpigmented red-to-brown
patches on face and upper trunk. To our knowledge, hyperpigmented
patches secondary to leukemia cutis is rarely described in the
literature.%
\end{abstract}%



\sloppy


\textbf{Leukemia Cutis presenting as Hyperpigmented patches. A rare
presentation}

Nastaran Namazi\textsuperscript{1}, Zahra Asadi Kani\textsuperscript{1},
Ali Kaddah\textsuperscript{2}, Reem Diab\textsuperscript{1*}

1. Skin Research Center, Shahid Beheshti University of Medical Sciences,
Tehran, Iran

2. Department of Surgery, Shohada-e Tajrish Hospital, Shahid Beheshti
University of Medical Sciences, Tehran, Iran

\textbf{*Corresponding author:}

Reem Diab (reemdiab1990@gmail.com)

Skin Research Center

Shahid Beheshti University of Medical Sciences,

Shohada-e Tajrish Hospital, Tehran, Iran

Tel: +9821 22741507-10

Fax: +9821 22744393

\textbf{Display Items: Figures Word Count:} 655

\textbf{Statements}

\textbf{Contributors} NN was involved in the diagnosis and management of
the patients and have been responsible for the clinical part of the
manuscript. ZAK reported the result of histopathological evaluation. NN,
RD and AK did literature review and drafted the manuscript. NN was
responsible for final editing of the manuscript, and coordinated the
study. All authors have read and approved the final manuscript.

\textbf{Patient consent for publication} Written informed consent was
obtained from the patient for publication of this case report and
accompanying images.

\textbf{Competing interests} the authors have no conflicts of interest
to declare.

\textbf{Funding Support} : This research did not receive any specific
grant from funding agencies in the public, commercial, or not-for-profit
sectors.

\textbf{ABSTARCT}

Leukemia cutis is a cutaneous manifestation of leukemia. Herein, we
present a rare cutaneous manifestation of leukemia cutis in a patient
with myeloid leukemia m5, characterized by hyperpigmented red-to-brown
patches on face and upper trunk. To our knowledge, hyperpigmented
patches secondary to leukemia cutis is rarely described in the
literature.

\textbf{KEY WORDS} Leukemia cutis, Leukemia, hyperpigmentation

\textbf{INTRODUCTION}

Leukemia is a potentially fatal and life-threatening neoplasm affecting
the hematopoietic system.\textsuperscript{1} Direct invasion of leukemic
neoplastic cells in the skin layers is named leukemia
cutis.\textsuperscript{1} Leukemia cutis is seen in various frequencies
in leukemia subtypes, but it is most commonly seen in acute
myelomonocytic leukemia (AML-4) and AML-M5 which have the highest rates
of skin manifestations.\textsuperscript{2} Approximately, about
2.9\%--3.7\% of AML cases present with leukemia
cutis.\textsuperscript{2}

We report a case of a 76-year-old man with skin rash who was diagnosed
later with acute myeloid leukemia (AML). The patient presented with
hyperpigmented patches on the face and upper trunk with ocular and oral
mucosal changes upon examination. Further workup revealed patient having
acute myeloid leukemia (AML-M5) and skin biopsy showed infiltration with
myeloblasts.

\textbf{CASE PRESENTATION}

A 76-year-old man with no significant past medical history presented to
our clinic with a six months skin hyperpigmentation and fatigue. The
patient was treated with skin-lightening and antisolar creams but with
no improvement. Clinical examination showed brown to violet
hyperpigmented patches on face and upper trunk. Mucosal examination
showed -violaceous plaques on the upper palate in addition to yellow
sclera with red to purple patches on the inner aspect of both lower
eyelids (figure 1). Physical examination showed lymphadenopathy
especially in axillary area. Laboratory evaluations revealed white blood
cell 4.6 \selectlanguage{ngerman}× 10 \textsuperscript{3} /L with neutrophil and lymphocyte
differentiation (18\% and 50\%, respectively), hemoglobin 10.5 g/dl and
platelet count of 72 × 10 \textsuperscript{3} \selectlanguage{greek}μ\selectlanguage{english}l.

Two skin biopsies from face and chest were taken with differential
diagnoses of angiosracoma, lymphoma, and lichen planus. The result
showed dense dermal multinodular perivascular and periadnexal
infiltration with atypical mononucleated cells with IHC evidence
consistent with leukemic dermal infiltration (figure 2).
Immunohistochemistry (IHC) staining was carried out according to
morphological findings and showed infiltrated cells with irregular
indented nuclei and high nuclear/cytoplasmic ratio which was positive
for leukocyte common antigen (LCA). No CD20, CD79a, CD3, CD45, CD30, MPO
or CD68 were detected in infiltrated cells. Clinical and
histopathological findings in addition to the flow cytometric
immunophenotyping of peripheral blood were compatible with myeloid
leukemia m5.

\textbf{DISCUSSION}

Patients with underlying hematologic malignancies can present with a
diversity of non-specific reactive skin lesions or specific
infiltrates.\textsuperscript{3} Leukemia cutis is a cutaneous
infiltration of neoplastic leukocytes which has multiple clinical
presentations including erythematous papules, nodules, plaques, bullae,
noduloulcerative lesions, and even erythroderma.\textsuperscript{3} The
lesions are often firm or/and hemorrhagic lesions.The most common
locations are face, head, neck, and trunk.\textsuperscript{3}

In addition to usual typical skin manifestations, the recorded unusual
manifestations of leukemia cutis were summarized in retrospective study
in 2021 by Yung-WeiChang which included leonine faces, figurate
cutaneous lesions, fingertip hypertrophy, erythema nodosum, guttate
psoriasis, chronic paronychia, leukemic vasculitis, and Sister Mary
Joseph's nodule.\textsuperscript{4}

Our patient was complaining of hyperpigmneted patches on the face and
upper trunk from six months before presenting to our clinic and
unfortunately the patches were treated as skin pigmentation.

Involvement of skin can be seen in any leukemia subtype, but most
commonly seen in acute myeloid leukemia (AML) with monocytic or
myelomonocytic and chronic lymphocytic leukemia (CLL), and rarely in
chronic myeloid leukemia (CML) which can be indicative for blast
transformation.\textsuperscript{5}

The diagnosis of leukemia cutis is usually achieved by histological
study and immunophenotyping.\textsuperscript{6} Histological findings
vary according to the type of leukemia, and most commonly present as
perivascular and periadnexal dermal
infiltrate.\textsuperscript{6,7}Additional occasional finding includes
stromal fibrosis, ulceration, dermal vessel thrombus, and subcutaneous
(7).

Currently, there is no specific treatment for leukemia cutis, and
cutaneous eruption usually resolves following treatment of underlying
leukemia (8).

To our knowledge, hyperpigmented patches secondary to leukemia cutis is
rarely described in the literature. Dermatologists could have an
important role in diagnosis of internal diseases including leukemia.
Postponing the diagnosis of leukemia cutis means delaying the diagnosis
of the underlying leukemia which lead to poor prognosis. Early diagnosis
of leukemia cutis can lead to better outcomes and may direct to an
underlying malignancy.

\textbf{REFERENCES}

1- Wasim Haidari, BS, BA; Lindsay C. Strowd, MD. Clinical
Characterization of Leukemia Cutis Presentation. Department of
Dermatology, Wake Forest School of Medicine, Winston-Salem, North
Carolina\emph{. CUTIS} . VOL. 104 NO. 6 I DECEMBER 2019

2- Dhauna Karam, Bharat Agrawal. Aleukemic Leukemia Cutis: Case Report
and Review of Literature. \emph{Indian J Med Paediatr Oncol} . 2018;
39(04): 443-445 DOI: 10.4103/ijmpo.ijmpo\_75\_17

3-Ambika Nohria, BA, Maressa C. Criscito, MD, Gillian K. Weston, MD,
Randie H. Kim, MD, PhD, Kristen I. Lo Sicco, MD, Alisa N. Femia, MD, et
al. Profound leukemia cutis in a patient with relapsed T-cell acute
lymphoblastic leukemia. \emph{JAAD Case Reports} . October 19, 2021,
DOI:https://doi.org/10.1016/j.jdcr.2021.10.013

4- Yung-WeiChang, Chih-HungLee, Han-ChiTseng. Leukemia cutis in a
medical center in southern Taiwan: A retrospective study of 42
patients.\emph{Journal of the Formosan Medical Association} . Volume
120, Issue 1, Part 1, January 2021, Pages 226-233

5- Parsi M, Go MS, Aadil Ahmed. Rush University Medical Center. Leukemia
Cutis\emph{. Europe PMC} . Book from StatPearls Publishing, Treasure
Island (FL), 15 May 2019 PMID: 31082180

6- Li Li,1 Yanan Wang,1 Christine Guo Lian,2 Nina Hu,2 Hongzhong Jin,1
and Yuehua Liu. Clinical and pathological features of myeloid leukemia
cutis. \emph{An Bras Dermatol} . 2018 Mar-Apr; 93(2): 216--221. doi:
10.1590/abd1806-4841.20186327

7- Manoj Gopal Madakshira1, Anuradha Bishnoi2, Dipankar De2, Man Updesh
Singh Sachdeva3, Uma Nahar Saikia. Leukemia cutis: A study from a
tertiary care hospital in North India. \emph{Indian journal of
dermatopathology and diagnostic dermatology} . 2020

8- Cesare Massone, Harry L. Winfield and Bruce R. Smoller. other
Lymphoproliferative and Myeloproliferative Diseases. SEC TION 18
NEOPLASMS OF THE SKIN. \emph{Bolongia dermatology} . 2018

\textbf{FIGURE LEGAND:}

\textbf{Figure 1. A, B, C:}

A: hyperpigmented patches on face and upper trunk.

B: violaceous plaques on the upper palate.

C: yellow sclera with red to purple patches on the inner aspect of lower
eyelid.

\textbf{Figure 2. A, B}

Dense perivascular and periadnexalnodular infiltrate of atypical
mononuclear cells in dermis.\selectlanguage{english}
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