\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Comment on: Primary Cutaneous Lymphomas in Children and Adolescents
Primary cutaneous follicle center lymphoma of the medial canthus of the
eye in an eleven year old}



\author[1]{Paul D'Alessandro}%
\author[2]{Andrea Lo}%
\author[3]{Martin Spencer}%
\author[2]{Pedro Farinha}%
\author[4]{Linlea Armstrong}%
\author[5]{Peter Dolman}%
\author[6]{Sylvia Cheng}%
\affil[1]{BC Children's Hospital}%
\affil[2]{British Columbia Cancer Research Centre}%
\affil[3]{Nanaimo Regional General Hospital}%
\affil[4]{British Columbia's Children's Hospital}%
\affil[5]{Eye Care Centre, Vancouver General Hospital}%
\affil[6]{B.C. Children's Hospital}%


\vspace{-1em}



  
  \date{June 13, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


\textbf{Comment on: Primary Cutaneous Lymphomas in Children and
Adolescents}

\textbf{Primary cutaneous follicle center lymphoma of the medial canthus
of the eye in an eleven year old}

Paul R. D'Alessandro, MD, MSc\textsuperscript{1}, Andrea C. Lo,
MD\textsuperscript{2}, Martin H. Spencer, MD\textsuperscript{3}, Pedro
Farinha, MD, PhD\textsuperscript{4}, Linlea Armstrong,
MD\textsuperscript{5}, Peter J. Dolman, MD\textsuperscript{6}, Sylvia
Cheng, MD\textsuperscript{1}

\textsuperscript{1}Division of Pediatric Hematology/Oncology/BMT,
British Columbia Children's Hospital, University of British Columbia,
Vancouver, British Columbia, Canada

\textsuperscript{2}Division of Radiation Oncology and Developmental
Radiotherapeutics, Department of Surgery, University of British
Columbia, British Columbia Cancer Agency, Vancouver, British Columbia,
Canada

\textsuperscript{3} Department of Ophthalmology, Nanaimo Regional
General Hospital, Nanaimo, British Columbia, Canada

\textsuperscript{4}Department of Pathology and Laboratory Medicine,
University of British Columbia, British

Columbia Cancer Agency, Vancouver, British Columbia, Canada

\textsuperscript{5}Department of Medical Genetics, University of British
Columbia, Children's and Women's Health Centre of BC, Vancouver, British
Columbia, Canada

\textsuperscript{6}Department of Ophthalmology \& Visual Sciences,
University of British Columbia, Vancouver General Hospital, Vancouver,
British Columbia, Canada

Corresponding Author:

Dr. Sylvia Cheng

Room B315, 4480 Oak Street, Vancouver, British Columbia, V6H 3V4

Phone~: 604.875.2406, Fax~: 604.875.2911, Email~: sylvia.cheng@cw.bc.ca

Word Count: Main Text: 462, not including Figures or References

Key Words: primary cutaneous follicle center lymphoma; pediatric;
ophthalmology

Abbreviations

PCFCL: primary cutaneous follicle center lymphoma, HHV8: human herpes
virus 8

To the Editor:

We present the fifth case of primary cutaneous follicle center lymphoma
(PCFCL) documented in a patient under age twenty-one. PCFCL is a
low-grade lymphoma of the follicle center B cells limited to skin
without systemic or nodal involvement at
diagnosis.\textsuperscript{1,2}Patients typically present with
localized, non-ulcerated, erythematous lesions on the scalp, forehead,
or trunk.\textsuperscript{1,3,4} PCFCL presenting on the lower extremity
carries a poorer prognosis.\textsuperscript{1,4} The etiology remains
unknown. Antecedent\emph{Borrelia burgdorferi} , hepatitis C, and human
herpes virus 8 (HHV8) infections have been
proposed.\textsuperscript{2,4}

Neoplastic lymphocytes in PCFCL are composed of centrocytes and
centroblasts derived from germinal center B
cells.\textsuperscript{3}These cells express B-cell and follicle center
markers, usually BCL6 and/or CD10.\textsuperscript{3,4} BCL2 expression
is variable, though usually absent.\textsuperscript{1,3} Ki-67
proliferation index may be low.\textsuperscript{1} Reactive T
lymphocytes are often seen.\textsuperscript{1,2,4} PCFCL is not usually
associated with BCL2 t(14;18.)\textsuperscript{1,2,3,4}

In adults, five-year progression free survival exceeds
95\%.\textsuperscript{2} Locally aggressive disease has been described
in untreated patients.\textsuperscript{1} Treatment for adult patients
includes surgical resection and/or radiation
therapy.\textsuperscript{2}Rituximab has been used for extensive
lesions.\textsuperscript{2,4}Transformation to diffuse large B-cell
lymphoma is uncommon.\textsuperscript{1} Recurrences, mostly
extracutaneous, occur in 20-30\% of patients.\textsuperscript{1,2,4} The
specific prognosis of pediatric PCFCL is unknown due to its
rarity.\textsuperscript{3}

The affected individual is an eleven-year-old male who presented with a
twelve-month history of an enlarging mass arising from the plica
semilunaris and caruncle in the medial canthus of his right eye (five mm
maximal diameter.) It was associated with keratoconjunctivitis sicca and
incomplete eyelid closure. The lesion was pink with central erythema. An
ophthalmologist excised the lesion with topical anesthetic without
complication. Pathology demonstrated PCFCL. Resection margin was
negative (Figure 1.) Chest x-ray, bone marrow aspirate/biopsy, MRI
brain/orbits, lumbar puncture with CSF analysis, and whole body
f-fluorodeoxyglucose (FDG) positron emission tomography were negative
for distant disease. Serologies for \emph{B burgdoferi} and hepatitis C
were negative. Imaging identified anatomic variants: fused C2-C3
vertebral bodies and posterior elements, right-sided aortic arch,
horseshoe kidney, bifid ribs, and thoracic hemivertebrae with levoconvex
curve. This patient was reviewed by a medical geneticist. There was no
clinical evidence of hereditary cancer syndrome. The family declined
whole exome sequencing.

Institutional multidisciplinary case conference recommended adjuvant
radiation therapy or observation. We elected for observation. The
patient remains disease-free at two years, with clinical exams by a
pediatric oncologist and ophthalmologist (every six months) and
pediatric dermatologist (annually.) This represents the fifth documented
case of pediatric PCFCL. Clinical features are consistent with the four
prior published cases.\textsuperscript{3,5,6,7,8} Those cases had
variable treatments, including surgery, with or without chemotherapy or
radiation therapy, and follow-up ranging from 13 to 48
months.\textsuperscript{5,6,7,8} Ceppi \emph{et al} advocate for
complete surgical resection of single lesions followed by observation
due to late effects of radiation.\textsuperscript{3} This patient's
outcome supports this conservative approach in a pediatric setting.

Figure 1: Polypoid fragment lined with non-keratinized squamous
epithelium with an atypical lymphoid infiltrate with nodular pattern
(Figure 1A, HE 2x.) The atypical lymphoid cells are variable in size
with small to medium centrocyte-like cells admixed with scattered larger
centroblast-like cells. Single cell necrosis and mitotic figures are
noted (Figure 1B, HE 40x.) The atypical cells are B-cells that express
strong CD20, CD10 and BCL6 as well as uniform BCL2. Fewer CD3+ T cells
are noted surrounding the nodular areas. The CD21 staining highlights
expanded and disrupted follicular dendritic cell meshwork consistent
with atypical follicles. The proliferation index of the B-cells (Ki-67)
is moderate, approximately 60\%. DNA PCR analysis using BIOMED2
immunoglobulin heavy chain gene consensus primers confirmed the presence
of a clonal B cell population (Figure 1C.) FISH analysis using Vysis
break-apart probes for the rearrangements of \emph{BCL2} and
\emph{BCL6}was negative.

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare.

ACKNOWLEDGEMENTS

The authors gratefully acknowledge the patient and his family for
supporting this publication.

ETHICS STATEMENT

The patient and his parents have consented to publication of this
clinical case.

REFERENCES

1. Skala SL, Hristov B, Hristov AC. Primary cutaneous follicle center
lymphoma. Arch Pathol Lab Med 2018;142:1313-1321.

2. Hamilton SN, Wai ES, Tan K, Alexander C, Gascoyne RD, Connors JM.
Treatment and outcomes in patients with primary cutaneous B-cell
lymphoma: The BC Cancer Agency experience. Int J Radiat Oncol Biol Phys
2013;87:719--725.

3. Ceppi F, Pope E, Ngan B, Abla O. Primary Cutaneous Lymphomas in
Children and Adolescents. Pediatr Blood Cancer 2016;63:1886-1894.

4. Coevic R, Jovanovic I, Kostovic K, Rados J, Dotlic S, Radman I,
Marinovic Kulisic S, Loncaric D. Radiotherapy of primary cutaneous
follicle center lymphoma: case report and review of literature. Radiat
Oncol 2013;8:147.

5. Condarco T, Sagatys E, Prakash AV, Rezania D, Cualing H. Primary
cutaneous B-cell lymphoma in a child. Fetal Pediatr Pathol
2008;27:206--214.

6. Ghislanzoni M, Gambini D, Perrone T, Alessi E, Beri E. Primary
cutaneous follicular center cell lymphoma of the nose with maxillary
sinus involvement in a pediatric patient. J Am Acad Dermatol.
2005;52:S73-S75.

7. Amitay-Laish I, Feinmesser M, Ben-Amitai D, David M, Manor Y, Kidron
D, Barzilai A, Hodak E. Juvenile onset of primary low-grade cutaneous
B-cell lymphoma. Br J Dermatol 2009;161:140--147.

8. Fink-Puches R, Chott A, Ardigo M, Simonitsch I, Ferrara G, Kerl H,
Cerroni L. The spectrum of cutaneous lymphomas in patients less than 20
years of age. Pediatric Derm 2004;21:525-533.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

