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\begin{document}

\title{Inflammatory myopathy in the proximal lower limb: Rare presentation of
lymphoma}



\author[1]{omid pourbagherian}%
\author[1]{Mehrzad Hajialilo}%
\author[1]{amir vahedi}%
\author[1]{Ali Esmaeili}%
\author[1]{Mehdi Jafarpour}%
\affil[1]{Tabriz University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\textbf{Inflammatory myopathy in the proximal lower limb: Rare
presentation of lymphoma}

Omid pourbagherian\textsuperscript{1}, Mehrzad
Hajialilo\textsuperscript{2}, Amir Vahedi\textsuperscript{3}, Ali
Esmaeili\textsuperscript{4}, Mehdi Jafarpour\textsuperscript{2}

\textsuperscript{1} Immunology Research Center, Tabriz University of
Medical Sciences, Tabriz, Iran

\textsuperscript{2}Connective Tissue Diseases Research Center, Tabriz
University of Medical Sciences, Tabriz, Iran

\textsuperscript{3}Department of Pathology, Tabriz University of Medical
Sciences, Tabriz, Iran.

\textsuperscript{4} Department of Pathology, Valiasr Hospital, Tabriz,
Iran.

Drafting of the manuscript: Omid pourbagherian, Mehrzad Hajialilo, Mehdi
Jafarpour

Data Collection: Mehrzad Hajialilo, Amir Vahedi, Ali Esmaeili, Mehdi
Jafarpour

Critical revision of the manuscript for important intellectual content:
Mehdi Jafarpour, Omid pourbagherian

Case supervision: Mehdi Jafarpour, Mehrzad Hajialilo

Corresponding author: Mehdi Jafarpour

Address: Connective Tissue Diseases Research Center, Flat 1, Imam Reza
Hospital, Tabriz, Iran

Phone number: 0098 41 33332704

Fax: 0098 41 35413520

Mobile: 09148651269

Keywords: \textbf{Inflammatory myopathy, lymphoma, inflammation, cancer}

Written informed permission from the patient to publish the facts and
photographs was granted.

\textbf{Introduction}

Inflammatory myopathy, myositis, refers to a category of uncommon
autoimmune disorders that entail~chronic~inflammation
and~muscular~weakness and
predominantly~target~the~musculoskeletal~system(1). The etiology of
inflammatory myopathy remains elusive; however, it is postulated that a
confluence of genetic susceptibility, environmental factors, and immune
response dysregulation may contribute to its manifestation(2, 3).

There are mainly 4 types of inflammatory myopathy: dermatomyositis (DM),
polymyositis (PM), overlap syndromes, and juvenile myositis(4).

The manifestation of DM is commonly observed through bilateral proximal
skeletal muscle weakness, which is frequently accompanied by distinctive
dermatological signs. A heliotrope flare-up localized on eyelids,
Gottron's papules, and periungual telangiectasia are the most prominent
symptoms of DM(5). The Bohan and Peter criteria are frequently utilized
in the diagnosis of dermatomyositis, incorporating a range of clinical,
laboratory, electromyography, and muscle biopsy assessments(6).

PM is characterized by muscle inflammation without significant skin
involvement(7). Overlap syndromes are characterized by the manifestation
of features that are common to both inflammatory myopathy and an
overlapping autoimmune disease. Organ involvement associated with
systemic lupus erythematosus (SLE) and skin manifestations may be
observed in patients(8).

Juvenile myositis encompasses inflammatory myopathies that occur in
children. Juvenile myositis in children may demonstrate the same
clinical presentations as adults, however, they may also manifest
distinct characteristics, such as high skin involvement and a greater
incidence of calcinosis(9).

Although the etiology of most cases of inflammatory myopathy remains
unknown or is attributed to autoimmune factors, there have been limited
reports of inflammatory myopathy presenting as an initial indication of
an underlying tumor(10).

\textbf{Case presentation}

A 43-year-old woman was admitted to our rheumatology outpatient clinic
with a primary complaint of lower limb edema and dyspnea on exertion.
Clinical findings in a hospitalized patient include: tachycardia (Heart
rate {[}HR{]} 110) , tachypnea (respiratory rate {[}RR{]} 26~per min),
blood pressure {[}BP{]} : 110/75, Body temperature: 38~, pale
conjunctiva, decrease in the intensity of heart sounds ,decreased breath
sounds at the base of the right lung and the left half of the chest, as
well as nonpitting edema in the right lower extremity with normal and
symmetric pulses .

The pericardial effusion and thickened pericardium were reported in the
echocardiography. The CT scan revealed left-sided pneumothorax and
right-sided pleural effusion. Additionally, collapse consolidation of
the lower lobes was reported in both lungs.

Abdominal ultrasound and Doppler ultrasound of the right lower limb
veins were reported as normal. Broad-spectrum antibiotics were initiated
for the patient, and they underwent pericardiocentesis. Pericardial
fluid drainage and pericardial biopsy were performed. The pericardial
fluid analysis showed exudative fluid with negative cultures, and no
malignant cells were observed in the cytology examination. The biopsy
results were consistent with pericardial fibrinosis. The patient was
discharged without a definitive diagnosis and was prescribed colchicine
medication.

During follow-up, the patient did not show improvement and continued to
experience palpitations and exertional dyspnea. Further investigations
were conducted, including CT angiography and CT scan of the abdomen and
pelvis, which were reported as normal. Cardiac magnetic resonance
imaging (MRI) was also performed, revealing thickened pericardium along
with signal changes in the ascending aorta. Considering the overall
findings, there is a possibility of rheumatological problems, and the
patient will undergo evaluation and examination by a rheumatologist.

Based on the further examinations, the patient has been diagnosed with
weakness (3/5) in the right lower extremity. Considering the signal
changes in the ascending aorta on the MRI, PET scan was performed. PET
scan findings include: several intense hypermetabolic foci in
pericardium, mild hypermetabolism in walls of ascending aorta.
Moderately hypermetabolic gastric wall thickening in the pylorus/antrum
regions. Diffuse intense hypermetabolism in muscles of neck, chest wall
and trunk abdomen, pelvis and right tight (especially in vastus
intermedius).

Based on the increased uptake in the muscles of the right thigh, further
investigations were requested for the muscles of the right leg and thigh
using MRI and electromyography (EMG)- NCS (Nerve Conduction Studies) for
the patient. The findings indicated inflammatory myopathy, and the MRI
results were reported as follows: diffuse muscular edema along right
tight muscles. Based on these findings, further tests were requested for
the patient to investigate the possibility of inflammatory myopathy.
)LDH: 1083/230UL , Aldolase : 33.5/7.6 U/L )(table 1)

The patient underwent muscle biopsy, which revealed severe inflammatory
myopathy with fascicular necrosis and prominent chronic fasciitis with
MHC1 markedly upregulated. (Fig 1\&2)

The patient was placed under treatment with IVIG (intravenous
immunoglobulin) and MTX (methotrexate) for a duration of 3 months for
the diagnosis of inflammatory myopathy. Subsequently, the patient
underwent corticosteroid therapy as part of the treatment plan.

The patient had a favorable response to treatment, and significant
clinical improvement was observed. However, due to severe hair loss,
methotrexate was discontinued, and Mycophenolate mofetil was started but
due to inadequate clinical response, patient was admitted to the
hospital to receive rituximab medication.

During the hospitalization, the patient developed acute abdominal
symptoms. Based on the imaging findings and examination, the diagnosis
of bowel perforation was suggested in the context of vasculitis. The
patient was scheduled for surgery, and a biopsy of the intestine was
obtained, which was consistent with high grade diffuse large B-cell
lymphoma.

The patient was referred to an oncologist for further management after
receiving this diagnosis. They were placed under the care of an
oncologist and started treatment with chemotherapy. The patient will
continue to be monitored and treated by the oncologist.

In the latest follow-up reports, the patient's condition remained
stable.

\textbf{DISSCUSSION}

The correlation between inflammatory myopathies and the occurrence of
cancer has been recognized for almost a century, yet its interpretation
and importance have remained ambiguous(11). Hill and colleagues have
published a comprehensive dataset that provides substantial evidence
regarding the association between myositis and malignancy(12). A total
of 618 individuals with dermatomyositis and 914 individuals with
polymyositis were successfully identified in the study. The incidence of
cancer was observed in approximately 30\% of patients with DM and 15\%
of patients with PM, with a notable majority of tumors being identified
subsequent to the initial diagnosis of myopathy.

The correlation between myopathies, which manifest as a component of a
paraneoplastic syndrome, and the presence of cancer is widely
acknowledged within the scientific community(13). Nevertheless, the
progress of epidemiological investigations in this area has been impeded
by limited sample sizes, the influence of referral bias, and
inconsistencies in diagnostic methodologies.

The spectrum of tumors linked to DM or PM mirrors the distribution
observed in the broader population, with the potential deviations being
a heightened occurrence of cervical(14), lung(15), ovarian(16),
pancreatic(17), bladder(18), and gastric carcinomas(19), as well as
non-Hodgkin lymphoma(20). The occurrence of cancer can be ascertained
prior to, during, or subsequent to the diagnosis of myositis, with a
notable surge in frequency observed within the two-year timeframe
encompassing the onset and progression of myositis. Furthermore, it is
worth noting that in certain individuals, the manifestation of myositis
is initially identified during a relapse of a previously diagnosed
neoplasm, whereas in other cases, myositis resurfaces coinciding with
the onset of evident malignancy. Our patient was diagnosed with
inflammatory myopathy based on clinical presentations. This specific
instance exemplifies the significance of possessing comprehensive
understanding regarding correlated paraneoplastic syndromes, as such
knowledge can prove instrumental in resolving infrequent yet critical
diagnostic dilemmas. The timely identification of malignancy is of
utmost importance in instances involving polymyositis. The acquisition
of any subtle indications that can assist clinicians in their diagnostic
endeavors is of utmost significance. Consequently, our investigation
underscores the criticality of contemplating neoplasms as a potential
differential diagnosis for patients who exhibit symptoms of myopathy.
Despite its infrequency, myopathy can manifest as the initial symptom
during presentation, thereby furnishing clinicians with a pivotal clue
that may facilitate an earlier identification of concealed malignancies.

\textbf{Conclusion}

In conclusion, our case presented a female with inflammatory myopathy
who presented a lymphoma, which is a rare underlying of lymphoma cancer.

\textbf{Acknowledgments}

The authors express their gratitude for the valuable contribution made
by the patient in providing biopsy and blood donation.

The authors appreciate support provided by Imam Reza Hospital, Tabriz,
Iran.

\textbf{Author contributions}

All authors approved the final manuscript.

\textbf{Availability of data and material}

Considering that this study is about a rare disease availability to
patients and data may hard to some extent.

\textbf{Funding}

Not applicable

\textbf{Competing interests}

The authors declare that they have no competing interests

\textbf{Corresponding author e-mail address~}

jafarpourmehdi1360@gmail.com

\textbf{Table 1: laboratory test findings}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
HBS Ag & Negative\tabularnewline
\midrule
\endhead
HCV Ab & Negative\tabularnewline
HIV Ab & Negative\tabularnewline
Mono test & Negative\tabularnewline
CMV IGM & Negative\tabularnewline
IGRA & Negative\tabularnewline
ESR & 30/20\tabularnewline
CRP & Negative\tabularnewline
F ANA & Negative\tabularnewline
C ANCA & Negative\tabularnewline
P ANCA & Negative\tabularnewline
Anti-smith ab & Negative\tabularnewline
Anti SSA & Negative\tabularnewline
Anti SSB & Negative\tabularnewline
Anti dsDNA & Negative\tabularnewline
Anti-centromere & Negative\tabularnewline
Wright & Negative\tabularnewline
Coombs wright & Negative\tabularnewline
C3 & 76 (90-180)\tabularnewline
C4 & 4 (10-40)\tabularnewline
Urine analysis & Normal\tabularnewline
Albumin & 3.7 (3.5-5.2)\tabularnewline
Creatinine & 0.8\tabularnewline
AST & 31\tabularnewline
ALT & 27\tabularnewline
ALKP & 144\tabularnewline
TSH & 2.8 (Normal)\tabularnewline
LDH & 1083/230 UL\tabularnewline
Aldolase & 33.5/7.6UL\tabularnewline
WBC & 8760\tabularnewline
HB & 11.2 g/dl\tabularnewline
MCV & 95\tabularnewline
PLT & 352000\tabularnewline
LYM & 14.5\%\tabularnewline
PMN & 68\%\tabularnewline
\bottomrule
\end{longtable}

\textbf{Figures}

\textbf{Fig 1:} A-E: BCL2, CD 20, c-MYC, KI67, and BCL6 expression in
lymphoma cancer by immunohistochemistry (IHC)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

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\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

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\end{figure}

\textbf{Fig 2} : Microscopic view (histologic) of a biopsy of the
intestine (A-C) (H\&E, \selectlanguage{ngerman}×10)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

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\end{figure}

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