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2696 1 12 15
Primary Thymic Hodgkin Lymphoma Coexisting
with Thymoma and Myasthenia Gravis:
A Case Report
BEF 1 Sarah Almuqbil
BEF 1 Amal AlHarbi
BEF 1 Fatimah S. Alzouri
ABEF 2 Hatem Yazeed Elbawab
BE 3 Noor S. Alsafwani
BE 3 Zahra Alkhunaizy
Corresponding Author: Sarah Almuqbil, e-mail: Saraalmoqbill@hotmail.com
Financial support: None declared
Conflict of interest: None declared
Patient: Female, 24-year-old
Final Diagnosis: Myasthenia gravis • thymic Hodgkin’s lymphoma • thymoma
Symptoms: Diplopia
Clinical Procedure: —
Specialty: Surgery
Objective: Rare disease
Background: Myasthenia gravis is a neuromuscular disorder that is strongly associated with thymoma. Although the pres-
ence of myasthenia gravis with other tumors is uncommon, approximately 50% of patients with thymoma
have myasthenia gravis. Thymic Hodgkin lymphoma should be considered due to the multiple reported cases
of patients with myasthenia gravis and Hodgkin lymphoma. In this report, we present the case of 24-year-old
woman with myasthenia gravis who was incidentally found to have coexisting thymoma with thymic Hodgkin
lymphoma.
Case Report: A 24-year-old woman with a known case of vitiligo presented with a 2-year history of diplopia and incidental
anterior mediastinal mass. Following investigations, myasthenia gravis was diagnosed and managed by pyr-
idostigmine, prednisolone, and azathioprine. Regarding the anterior mediastinal mass, thymoma was suspect-
ed based on the presence of myasthenia gravis and radiological findings. She underwent extended transsternal
thymectomy. The final histopathological report of the dissected thymus disclosed Hodgkin lymphoma pathol-
ogy coexisting with thymoma. After the diagnosis of Hodgkin lymphoma nodular sclerosis type IIA was con-
firmed, 6 cycles of chemotherapy were administered. Four years of follow-up revealed no evidence of Hodgkin
lymphoma. However, her symptoms of myasthenia gravis persisted despite Hodgkin lymphoma remission.
Conclusions: There is an unclear association between myasthenia gravies and Hodgkin lymphoma. Prior reports revealed
regression of myasthenia gravies following Hodgkin lymphoma management, which suggests that myasthe-
nia could be a complication of Hodgkin lymphoma. However, in our case, myasthenia gravis persisted after
Hodgkin lymphoma management; therefore, further studies are needed to explore this association.
Keywords: Hodgkin Disease • Myasthenia Gravis • Thymoma • Mediastinal Neoplasms •
Paraneoplastic Syndromes
Full-text PDF: https://www.amjcaserep.com/abstract/index/idArt/941792
Authors’ Contribution:
Study Design A
Data Collection B
Statistical Analysis C
Data Interpretation D
Manuscript Preparation E
Literature Search F
Funds Collection G
1 College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam,
Saudi Arabia
2 Thoracic Surgery Division, Department of Surgery, College of Medicine, Imam
Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
3 Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal
University, Dammam, Saudi Arabia
e-ISSN 1941-5923
© Am J Case Rep, 2023; 24: e941792
DOI: 10.12659/AJCR.941792
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Background
Thymoma is an anterior mediastinal tumor derived from the
epithelial cell of the thymus. It is the most common mass of
the anterior mediastinum [1]. Thymoma has a strong relation-
ship with paraneoplastic syndromes, particularly myasthenia
gravis, which is an autoimmune disorder that affects acetyl-
choline receptors at the neuromuscular junction in the skele-
tal muscle [1]. Patients with myasthenia gravis tend to present
with ocular, bulbar, and limb muscles weakness, and approxi-
mately 50% of patients with thymoma experience symptoms
suggestive of myasthenia gravis [1].
Hodgkin lymphoma is a monoclonal lymphoid tumor that
commonly affects mediastinal lymph nodes [2,3]. Primary thy-
mic Hodgkin lymphoma affection without lymphadenopathy
is rare [3]. While myasthenia gravis is frequently associated
with thymoma, its relationship with other anterior mediasti-
nal tumors, particularly primary thymic Hodgkin lymphoma,
is rarely reported [4].
To the best of our knowledge, only 5 cases reported the associ-
ation between myasthenia gravis and thymic Hodgkin lympho-
ma, as summarized in Table 1. Null et al documented a case of
a young woman with myasthenia gravis who had a history of
fatigue, hand weakness, and difficulty chewing [5]. In that case,
myasthenia gravis was associated with an anterior mediastinal
mass on chest radiography, and initially thymoma was suspect-
ed [5]. After thymectomy, the diagnosis of isolated primary thy-
mic Hodgkin lymphoma of nodular sclerosing type, stage IA was
confirmed. Surgical resection of the thymic lesion was followed
by complete remission of myasthenia gravis symptoms. The pa-
tient underwent 2 courses of radiotherapy as well [5]. Similarly,
Tranchant et al reported a young woman who presented with
Case Age Sex Myasthenia
gravis
Anti-
receptor
Antibody
Hodgkin
lymphoma
presentation
Hodgkin
lymphoma
type
Hodgkin
lymphoma
Stage
Treatment Outcome
Null et al,
1977 [5]
19 F Generalized
fatigue, hand
weakness,
difficulty
chewing
– Chest X-ray
shows
anterior
mediastinal
mass
Nodular
sclerosing
type
IA – Thymectomy
– Radiation
therapy
Remission of
both MG and
HL
Tranchant
et al,
1993 [6]
29 F Weakness of
upper limbs,
neck,
and larynx
Negative CT shows
anterior
mediastinal
mass
Nodular
sclerosing
type
IIB – Thymectomy
– Three cycles of
chemotherapy
– Radiation
therapy
Remission
of HL
MG initially
got worse then
improved
Ferrò et al,
2005 [7]
52 F Generalized MG Positive CT and MRI
show anterior
mediastinal
mass
Nodular
sclerosing
type
IIA – Thymectomy
– Three cycles of
chemotherapy
– Five cycles of
chemotherapy
– Radiation
therapy
Remission of
both MG and
HL
Ayadi-
Kaddour
et al,
2008 [8]
22 M Asymptomatic
(diagnosed by
electromyo-
graphy)
–– Presented
with
thoracic
symptoms
– CT shows
antero-
superior
mediastinal
mass
– – – Thymectomy
– Chemotherapy
Remission of
MG
Yousfi et al,
2021 [9]
22 F Weakness,
fatigue, and
ptosis
Positive CT shows
anterior
mediastinal
mass
Mixed
cellularity
IIIA – –
Table 1. Reported cases of myasthenia gravis associated with Hodgkin lymphoma.
F – female; M – male; CT – computed tomography; MRI – magnetic resonance imaging; HL – Hodgkin lymphoma; MG – myasthenia
gravis.
Almuqbil S. et al:
Thymic Hodgkin lymphoma with thymoma and myasthenia gravis
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upper limb, neck, and larynx weakness and was diagnosed with
seronegative myasthenia gravis [6]. In that case, a computed to
-
mography (CT) scan showed an anterior mediastinal mass, and
the lesion was resected. The pathology report revealed thymic
Hodgkin lymphoma of nodular sclerosing type, stage IIB. After
the surgical resection of thymus, she was given 3 cycles of che-
motherapy, and radiotherapy was provided later. Initially after
Hodgkin lymphoma treatment, she experienced worsening of
myasthenia gravis symptoms, but then the symptoms start-
ed to improve slowly, and the corticosteroid was stopped [6].
Additionally, Ferrò et al reported a middle-aged female patient
diagnosed with seropositive generalized myasthenia gravis [7].
After starting medical treatment of myasthenia gravis, radio-
logical imaging suggested thymoma. The patient underwent
thymectomy, and the tissues sent for cytopathology analysis
showed thymic Hodgkin lymphoma of nodular sclerosing type,
stage IIA [7]. The symptoms of myasthenia gravis resolved, with
a significant decrease of anti-nicotinic acetylcholine receptors
following the surgical resection, chemotherapy, and radiother-
apy [7]. Moreover, Ayadi-Kaddour et al reported a young male
patient who presented with thoracic symptoms [8]. Chest ra-
diography and CT showed an anterior mediastinal mass. Since
thymoma was suggested, electromyography was performed.
Electromyography showed signs of myasthenia gravis, although
the patient was asymptomatic. Thymectomy was performed,
and thereafter the pathology report showed thymic Hodgkin
lymphoma. Myasthenia gravis completely regressed after sur-
gical treatment. The patient also received complementary che-
motherapy afterward [8]. Lastly, in 2021, Yousfi et al reported
a young female patient who presented with fatigue, weakness,
and ptosis [9]. The diagnosis of seropositive myasthenia gravis
was confirmed. Chest CT showed anterior mediastinal mass.
Two months later, the patient presented with cervical lymph-
adenopathy [9]. A biopsy was taken and showed the mixed cel-
lularity type of Hodgkin lymphoma [9]. A positron-emission to-
mography scan showed an anterior mediastinal mass as well as
supradiaphragmatic and subdiaphragmatic lymphadenopathy.
Hodgkin lymphoma was staged as IIIA, since the patient was
not experiencing constitutional symptoms. Unfortunately, the
management and outcome were not discussed in the report [9].
The association between myasthenia gravis and Hodgkin lym-
phoma has not yet been clarified. This report represents a
24-year-old female patient who was diagnosed with a case of
myasthenia gravis along with an incidental anterior mediasti-
nal mass that was later confirmed to be Hodgkin lymphoma
coexisting with thymoma.
Case Report
A 24-year-old female patient with a known case of vitiligo
was admitted as a case of an incidental anterior mediastinal
mass found on a routine chest radiograph (Figure 1). She had
a 2-year history of diplopia, yet she did not seek medical ad-
vice before. The patient denied any history of muscle weak-
ness, dysphagia, dyspnea, chest pain, night sweats, weight
loss, or fever. The family history was insignificant, including
no history of malignancy or myasthenia gravis. Physical ex-
amination was unremarkable, and lymph nodes were impal-
pable. Laboratory tests showed an elevated erythrocyte sed-
imentation rate of 44 mm/h and a C-reactive protein level
of 1.6 mg/dL.
During admission, myasthenia gravis was diagnosed, which
was confirmed by an electromyography test. Treatment be-
gan with oral pyridostigmine 60 mg administered 4 times per
day, oral prednisolone 10 mg once daily, and oral azathioprine
100 mg once daily.
A chest CT scan with contrast was performed for further as-
sessment of the mass (Figure 2). It showed a 3.7×5.4×7.2 cm
homogenous anterior mediastinum soft tissue mass with a
clear fat plane separating the mass from the vascular structure,
which suggested a diagnosis of thymoma, with consideration of
other differential diagnoses, such as lymphoma and teratoma.
The patient underwent median sternotomy, and complete dis-
section of the mass, mediastinal fat, and thymus gland was
performed (Figure 3). Macroscopically, the specimen consisted
of a tan-brown, rubbery, and lobulated thymus, weighing 93 g
and measuring 9.0×8.0×3.5 cm. Sectioning showed a white-yel-
low lobulated cut surface with scattered cysts (Figure 4). An in-
tra-thymic lymph node was identified and measured 1.2×1 cm.
Figure 1. Anteroposterior chest radiograph shows an anterior
mediastinal mass.
Almuqbil S. et al:
Thymic Hodgkin lymphoma with thymoma and myasthenia gravis
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Microscopically, hematoxylin and eosin–stained sections showed
variably sized nodules surrounded by fibro-collagenous bands.
Areas of high cellularity had scattered large atypical neoplastic
cells. Several variants of these Reed-Sternberg like cells were
present, including mononuclear Hodgkin cells, multinucleat-
ed Reed-Sternberg cells, lacunar cells, and mummified cells
(Figure 5). They aggregated in confluent sheets in some ar-
eas (syncytial growth pattern). The background consisted of
non-neoplastic polymorphic inflammatory cells with predomi-
nance of neutrophils, lymphocytes, plasma cells, and eosinophils
(Figure 6). Thymic tissue was illustrated by the presence of
large epithelial cells and prominent Hassall corpuscles. Some of
these corpuscles were surrounded and infiltrated by Hodgkin
cells (Figure 7). Additionally, the existence of numerous cysts
lined by various types of epithelium and large medullary ger-
minal centers (thymic hyperplasia) was confirmed (Figure 8).
One lymph node showed Hodgkin lymphoma.
Figure 2. Contrast-enhanced chest computed tomography shows
homogeneous anterior mediastinal soft tissue mass,
with no vascular involvement. Figure 4. Gross pathological specimen shows yellow mutli-
lobulated cut surface of the thymus with cyst
formation (immunohistochemistry, original
magnification 200×).
Figure 5. Scanning magnification shows variable sized nodules
surrounded by fibrous collagen bands with adjacent
thymic epithelial cyst (immunohistochemistry, original
magnification 100×).
Figure 3. Grossly brown and lobulated thymus that weighed 93
g and measured 9×8×3.5 cm.
Almuqbil S. et al:
Thymic Hodgkin lymphoma with thymoma and myasthenia gravis
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Immunohistochemistry stains revealed expression of CD15 and
CD30 antigens by the Hodgkin cells, with the membranous and
perinuclear (Glogi) staining patterns (Figure 9). However, they
lacked CD45 expression and some of them showed weak mem-
branous positivity for CD20. In the background, mixed reactivity
of CD3 and CD5 was demonstrated (background T cells). Thymic
epithelial cells showed membranous positivity for cytokeratin
19 (CK19) and focal membranous positivity for pan-cytoker-
atin (pan-CK) in an arborizing pattern (Figures 10, 11). They
also showed nuclear positivity for protein 63 (P63) (Figure 12).
The strong reactivity for CK19 and P63 with focal positivity for
pan-CK denoted background thymoma. All immunohistochem-
ical tests were performed on formalin-fixed (6-72 h) paraffin-
embedded sections using the ultraview universal DAB detec-
tion system from FDA-approved Ventana.
The pathological diagnosis was classic Hodgkin lymphoma,
nodular sclerosis subtype, syncytial variant, with background
thymoma, and possible thymic follicular hyperplasia.
Figure 6. Reed-Sternberg cells and Hodgkin cell variants with
polymorphic cells background (immunohistochemistry,
original magnification 100×).
Figure 8. Thymic epithelial hyperplasia (immunohistochemistry,
original magnification 100×).
Figure 9. Membranous and perinuclear staining pattern for
CD15 in thymic Hodgkin and Reed-Sternberg cells
(immunohistochemistry, original magnification 200×).
Figure 7. Hassall corpuscle surrounded by Hodgkin cells
(immunohistochemistry, original magnification 100×).
Almuqbil S. et al:
Thymic Hodgkin lymphoma with thymoma and myasthenia gravis
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Clinically, it was staged as IIA Hodgkin lymphoma, according
to the Cotswold classification. She was treated with 6 cycles
of the ABVD chemotherapy protocol (doxorubicin, vinblastine,
bleomycin, and dacarbazine). At present, after 4 years from
surgical management, no evidence of Hodgkin lymphoma was
detected during the follow-up. Regarding her ocular symptoms,
after a latent period of 3.5 years, worsening of her symptoms
was noticed in the postpartum period, which required dosage
adjustment of her medications.
Discussion
Herein, we describe the case of a 24-year-old woman who had
an incidental anterior mediastinal mass on a routine chest ra-
diograph and 2-year history of diplopia. Myasthenia gravis was
diagnosed, and the patient was treated with pyridostigmine,
prednisolone, and azathioprine. Further assessment by a chest
CT scan revealed a homogenous anterior mediastinum soft
tissue mass, suggestive of thymoma, lymphoma, and terato-
ma. Surgical removal was performed, and the histopathology
report revealed classic Hodgkin lymphoma, nodular sclerosis
subtype, syncytial variant, with possible thymic follicular hy-
perplasia and background of thymoma. She received chemo-
therapy, and presently, after 4 years of follow-up, no evidence
of Hodgkin lymphoma was detected. However, she experienced
worsening ocular symptoms in the postpartum period, requir
-
ing medication adjustment.
Myasthenia gravis prevalence is estimated to be 12.4 individ-
uals per 100 000 globally [10]. Myasthenia gravis is defined
as an autoimmune-mediated antibody disorder in which post-
synaptic membrane components of the skeletal muscle fibers
are attacked [11,12]. This attack leads to different symptoms,
which vary among patients and include fluctuating ocular, bul-
bar, and limb skeletal muscle weakness [12]. This weakness can
be generalized or specific to certain muscle groups, leading to
various symptoms that depend on the involved muscles [12].
More than three-quarters of patients present initially with ex-
tra-ocular muscle weakness, such as diplopia and ptosis [12].
Bulbar muscle weakness can present initially in a much low-
er proportion of patients as dysphagia, flaccid dysarthria, and
hoarseness [12]. In myasthenia gravis, limb weakness usual-
ly affects proximal muscles with upper limbs more than distal
muscles and lower limbs [12].
Figure 10. Membranous staining on an arborizing pattern for
cytokeratin 19 with prominent in between negative
lacunar cells (immunohistochemistry, original
magnification 100×).
Figure 12. Nuclear positivity for protein 63
(immunohistochemistry, original magnification 100×).
Figure 11. Focal membranous positivity for pan-cytokeratin
(immunohistochemistry, original magnification 200×).
Almuqbil S. et al:
Thymic Hodgkin lymphoma with thymoma and myasthenia gravis
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Myasthenia gravis occurs in individuals who are genetically
susceptible [4]. Precipitated factors include surgeries, drugs,
infections, pregnancy, and immunization [12]. The pathophysi-
ology of myasthenia gravis depends on the type of antibodies
involved [10-12]. These antibodies act on nicotinic acetylcho-
line receptors (n-AChRs), lipoprotein-related protein 4 (LPR4),
and muscle-specific kinase to prevent binding of acetylcho-
line to its receptor and inhibit n-AChR distribution and clus-
tering [10-12]. These antibodies contribute to the diagnosis of
myasthenia gravis, especially anti-nicotinic acetylcholine recep-
tors [12]. Patients with generalized and pure ocular myasthe-
nia gravis present with 80% and 50% positive anti-n-AChRs,
respectively [12]. In patients who are seronegative for antibod-
ies, electrophysiologic tests including single-fiber electromy-
ography and repetitive nerve stimulation tests used to assess
conduction delay in myasthenia gravis [12]. Myasthenia gra-
vis manifests either as an autoimmune disease or as a para-
neoplastic syndrome related to thymus tumors but is rarely
reported with other tumors [13]. Pathological changes of the
thymus are shown in most patients with n-AChR antibodies
and in a portion of patients with LRP4 antibodies but rarely in
muscle-specific kinase antibodies [13]. Early onset myasthenia
gravis is frequently related to thymus lymphofollicular hyper-
plasia, while the late onset exhibits age-related thymic invo-
lution [13]. In contrast, approximately 15% of patients have
thymoma-associated myasthenia gravis [13]. These findings of
thymic epithelial hyperplasia indicate the involvement of the
thymus in the production of antibodies against the muscle re-
ceptors [13]. Management of symptomatic myasthenia gravis
consists of acetylcholinesterase inhibitors; immunosuppres-
sants, mainly glucocorticoids, can be added in case of persis-
tent symptoms [12]. Intravenous immunoglobulin is beneficial
in case of a myasthenic crisis [12]. Patients with early onset my
-
asthenia gravis, thymoma associated with myasthenia gravis,
or seronegative antibody are indicated for thymectomy [12].
Thymoma is an anterior mediastinum mass originating from
the epithelial cells of the thymus, which can be discovered in-
cidentally or through symptoms [1]. The presenting symptoms
of thymoma are caused by paraneoplastic syndrome or are due
to compression against adjacent organs leading to symptoms
such as dyspnea, chest pain, or cough [1]. Myasthenia gra-
vis is the most common paraneoplastic syndrome associated
with thymoma; approximately 50% of patients with thymoma
have myasthenia gravis [1]. However, patients with symptom-
atic myasthenia gravis are diagnosed earlier, so thymoma is
discovered in less advanced stages [1]. The modalities used in
diagnosis of thymoma are chest CT or MRI; however, the de-
finitive diagnosis needs tissue that is obtained either by sur-
gical resection or biopsy [1].
Hodgkin lymphoma is a monoclonal lymphoid neoplasm and
rare malignancy with an estimated incidence rate of 2.6 cases
per 100 000 individuals in the United States [2]. It is divid-
ed into 2 categories: classical Hodgkin lymphoma and nodu-
lar lymphocyte-predominant Hodgkin lymphoma [2]. These 2
categories show differences in pathology and clinical presen-
tation [12]. Classical Hodgkin lymphoma represents 95% of
all Hodgkin lymphoma cases, which are further divided into 4
subtypes: lymphocyte-rich, lymphocyte-depleted, mixed cellu-
larity, and nodular sclerosis Hodgkin lymphoma [2]. The pre-
cise cause of Hodgkin lymphoma is unknown. However, the
risk of Hodgkin lymphoma increases in autoimmune diseas-
es, immunosuppression, and Epstein-Barr virus infection [2].
Also, there is evidence of familial predisposition in Hodgkin
lymphoma [2]. Patients with Hodgkin lymphoma often pres-
ent with painless supradiaphragmatic lymphadenopathy and
B symptoms including high fever, unexplained weight loss,
and profuse night sweats [2]. If the enlargement of the medi-
astinal lymph nodes is significant, the mass effect can cause
shortness of breath and chest pain [2]. In patients with extra-
nodal disease, related clinical manifestations can occur [2].
Hodgkin lymphoma often involves the intrathoracic structure,
mediastinal lymph nodes in particular [3]. Thymus gland in-
volvement is reported, but the exact prevalence is unknown [3].
It is uncommon to have Hodgkin lymphoma of the thymus
gland without lymphadenopathy [3]. Heron et al discovered
30% thymic enlargement in 50 patients with thoracic disease
on CT scans [3]. All these patients with thymic enlargement
at the time of diagnosis also had enlarged mediastinal lymph
nodes [3]. Moreover, the frequency of thymic enlargement was
higher (56%) in the series of Wernecke, in which there were
only 6 cases of isolated thymic enlargement among 43 pa-
tients with newly diagnosed Hodgkin lymphoma [3]. Patients
with thymic Hodgkin lymphoma are often asymptomatic un-
til extrathymic disease develops [3].
Patients with myasthenia gravis show an increased risk of extra-
thymic neoplasms, triple that of those who do not undergo thy-
mectomy [14]. The only case reported of extrathymic Hodgkin
lymphoma with myasthenia gravis was of a 44-year-old wom-
an with ocular, bulbar, and limb muscle weakness that was di-
agnosed as myasthenia gravis with n-AChR antibody, which
was managed with pyridostigmine [15]. In the same year, the
patient presented with a left anterior neck mass, which was
diagnosed after 3 years of her presentation of lymphoma with
mixed cellularity. In this case, lymphoma was treated with 6
cycles of chemotherapy, and the patient noticed the resolution
of her myasthenic symptoms, the n-AChR antibody level de-
clined, and her myasthenia gravis medication was ceased [15].
To the best of our knowledge, only 5 cases have reported the
association between myasthenia gravis and thymic Hodgkin
lymphoma [5-9]. According to the reported cases, myasthe-
nia gravis associated with thymic Hodgkin lymphoma is more
Almuqbil S. et al:
Thymic Hodgkin lymphoma with thymoma and myasthenia gravis
© Am J Case Rep, 2023; 24: e941792
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common in females, as 4 of 5 cases were female patients, which
is similar to the present case [5-9]. The presentation of myas-
thenia gravis in the previous cases varies, with most of them
having muscle weakness in addition to bulbar or ocular symp-
toms, specifically ptosis, while our patient presented with just
mild diplopia [5-7,9]. However, 1 patient was asymptomatic for
myasthenia gravis and presented with thoracic symptoms [8].
Pathological reports of the previous cases revealed a domina-
tion of nodular sclerosing Hodgkin lymphoma, with 3 patients
in addition to our own having this diagnosis [5-8]. Mixed cel-
lularity Hodgkin lymphoma was observed in only 1 case [9].
Different stages of Hodgkin lymphoma were exhibited in the
reported cases, in which 2 were stage II and the others were
stage I and III [5-9].
Regarding the management of the cases, most of the patients
underwent thymectomy followed by chemotherapy [6-9]. In
2 cases, chemotherapy was stopped due to adverse effects
and was replaced with radiation therapy [6,7]. The first case,
described in 1977, was the only case managed by radiation
therapy in addition to thymectomy [5]. After thymectomy, re-
mission of Hodgkin lymphoma as well as myasthenia gravis
symptoms was noticed in all previous cases, in contrast to the
present case, which had a latent period of 3.5 years, followed
by the worsening of myasthenia gravis symptoms in the post-
partum period [5-9].
Conclusions
The association between myasthenia gravis and Hodgkin lym-
phoma is still unclear. In contrast to this report, the complete
remission of myasthenia gravis after the management of
Hodgkin lymphoma in previous reports led to the conclusion
that myasthenia gravis could be a complication or paraneo-
plastic syndrome of Hodgkin lymphoma. It is suggested that
research efforts be focused on examining this area in order
to understand the relationship between Hodgkin lymphoma
and myasthenia gravis.
Department and Institution Where Work Was Performed
Department of Surgery, College of Medicine, Imam Abdulrahman
Bin Faisal University, Dammam, Saudi Arabia.
Declaration of Figures’ Authenticity
All figures submitted have been created by the authors who
confirm that the images are original with no duplication and
have not been previously published in whole or in part.
References:
1. Robinson SP, Akhondi H. Thymoma. [Updated 2023 Jul 17]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
Available from: https://www.ncbi.nlm.nih.gov/books/NBK559291/
2. Kaseb H, Babiker HM. Hodgkin lymphoma. [Updated 2023 Jun 26]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
Available from: https://www.ncbi.nlm.nih.gov/books/NBK499969/
3. Wajdi K, Sameh M, Salma F, et al. Primary Hodgkin’s disease of the thy-
mus. Respir Med CME. 2010;3(1):15-17
4. Dresser L, Wlodarski R, Rezania K, Soliven B. Myasthenia gravis: Epidemiology,
pathophysiology and clinical manifestations. J Clin Med. 2021;10(11):2235
5. Null JA, Livolsi VA, Glenn WW. Hodgkin’s disease of the thymus (granulo-
matous thymoma) and myasthenia gravis: A unique association. Am J Clin
Pathol. 1977;67(6):521-25
6. Tranchant C, Racamier E, Warter JM. Seronegative myasthenia gravis and
familial Hodgkin’s disease. Eur Neurol. 1993;33(1):17-19
7. Ferrò MT, Riccardi T, Montanelli A, et al. Myasthenia gravis remission and an-
ti-AChR ab reduction after immunosuppressive and anti-neoplastic therapy
in a patient with thymic Hodgkin’s disease. J Neurol. 2006;253(9):1241-42
8. Ayadi-Kaddour A, Mlika M, Kilani T, El Mezni F. A primary mediastinal
Hodgkin’s lymphoma with asymptomatic myasthenia gravis: A rare asso-
ciation. Pathologica. 2008;100(3):170-72
9. Yousfi J, Bensalek F, Zahlane M, et al. Myasthenia gravis revealing Hodgkin’s
lymphoma. Eur J Case Rep Intern Med. 2021;8(3):002375
10. Salari N, Fatahi B, Bartina Y, et al. Global prevalence of myasthenia gravis
and the effectiveness of common drugs in its treatment: A systematic re-
view and meta-analysis. J Transl Med. 2021;19(1):516
11. Phillips WD, Vincent A. Pathogenesis of myasthenia gravis: Update on dis-
ease types, models, and mechanisms. F1000Res. 2016;5: F1000 Faculty
Rev-1513
12. Beloor Suresh A, Asuncion RMD. Myasthenia gravis. [Updated 2023 Aug 8].
In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
Available from: https://www.ncbi.nlm.nih.gov/books/NBK559331/
13. Melzer N, Ruck T, Fuhr P, et al. Clinical features, pathogenesis, and treat-
ment of myasthenia gravis: A supplement to the Guidelines of the German
Neurological Society. J Neurol. 2016;263(8):1473-94
14. Papatestas AE, Osserman KE, Kark AE. The relationship between thymus
and oncogenesis. A study of the incidence of non thymic malignancy in
myasthenia gravis. Br J Cancer. 1971;25(4):635-45
15. Abrey LE. Association of myasthenia gravis with extrathymic Hodgkin’s lym-
phoma: Complete resolution of myasthenic symptoms following antineo-
plastic therapy. Neurology. 1995;45(5):1019
Almuqbil S. et al:
Thymic Hodgkin lymphoma with thymoma and myasthenia gravis
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